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single-nucleotide polymorphism rs2275294 in ZNF512B is not Associated with Susceptibility to Amyotrophic Lateral Sclerosis in a Large Chinese Cohort

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Chinese Medical Journal 2015年第24期128卷 3305-3309页

作者： Xiao-Dong Ju Tao Liu Jing Chen Xiao-Gang Li Xin-Xiu Liu Wen-Chao Liu Kai Wang Min Deng Institute of Sports Medicine Peking University Third Hospital Beijinq 100191 China Medical Research Center Peking -UniversityThird Hospital Beijing 100191 China Department of Bioscience College of Life Science North China University of Science and Technology Tangshan Hebei 063000 China Department of Neurology Peking University Third Hospital Beijing 100191 China Department of Neurology The First Affiliated Hospital of Anhui Medical University Hefei Anhui 230022 China

Background： Amyotrophic lateral sclerosis （ALS） is a fatal neurodegenerative disease that primarily affects motor neurons and has no effective treatment. Recently, Iida et al. identified a single-nucleotide polymorphism （SNP） rs2275294 in the ZNF512B gene that is significantly associated with susceptibility to ALS in the Japanese population. Here, we performed a case-control study examining the possible association of rs2275294 with risk of sporadic ALS （SALS） in a large Chinese cohort. Methods： To assess this association, we performed a replication study in 953 SALS patients and 1039 age- and gender-matched healthy control subjects, who were recruited from Peking University Third Hospital and the First Affiliated Hospital of Anhui Medical University from January 2004 to December 2013 throughout China. We genotyped the rs2275294 SNP using polymerase chain reaction and direct sequencing. Results： The allele frequency of rs2275294 in ZNF512B was different between Japanese and Chinese. The association in Chinese between ALS patients and controls did not reach statistical significance （P = 0.54; odds ratio = 0.94; 95% confidence interval = 0.76-1.15）. Conclusions： The SNP rs2275294 in ZNF512B is not considered to be associated with ALS susceptibility in the Chinese population. Our study highlights genetic heterogeneity in ALS susceptibility in different population. Given our negative results, further replication study involving larger and more homogeneous samples in different ethnicities should be performed in the future.

关键词： Amyotrophic Lateral Sclerosis Genome Association Study single-nucleotide polymorphism ZNF512B

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Prevalent false positives of azoospermia factor a （AZFa） microdeletions caused by single-nucleotide polymorphism rs72609647 in the sY84 screening of male infertility

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Asian Journal of Andrology 2011年第6期13卷 877-880页

作者： Qing Wu Guo-Wu Chen Tao-Fei Yan Hui Wang Yu-Ling Liu Zheng Li Shi-Wei Duan Fei Sun Yun Feng Hui-Juan Shi Reproductive Medical Center Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 China Shanghai Jiai Genetics and IVF Institute Center of China-USA Shanghai 200011 China Department of Obstetrics and Gynecology Second Military Medical University Shanghai 200433 China China National Population and Family Planning Key Laboratory of Contraceptive Drugs and Devices Shanghai Institute of Planned Parenthood Research Shanghai 200032 China Shanghai Human Sperm Bank Shanghai Institute of Andrology Renji Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200001 China School of Medicine Ningbo University Ningbo 315033 China Laboratory for Reproductive Biology School of Life Science University of Science and Technology of China Hefei 230026 China

Multiplex polymerase chain reaction （PCR） has been widely used to detect Y-chromosome micredeletions, which is one of the major causes of male infertility. Both the European Academy of Andrology （EAA） and the European Molecular Genetics Quality Network （EMQN） have recommended the use of sY84 and sY86 markers for the detection of azoospermia factor a （AZFa） microdeletion during DNA testing for male infertility. In this study, a large-scale analysis of AZF microdeletion in a total of 630 Chinese males, including healthy semen donors （n=200）, infertile males with normal sperm count （n=226） and patients with either nonobstructive azoospermia or severe oligozoospermia （n=204）, was performed. A series of nine sequence-tagged site （STS） markers from the AZF region of the Y chromosome was used to detect microdeletions. All primers were designed based on the recommendations of the National Center for Biotechnology Information. An unusually high incidence （73/630, 11.6%） of sY84-absent but sY86-present genotypes was observed in the AZFa microdeletion screening. Sequencing the sY84-flanking region revealed a total of 73 patients with sY84-absent but sY86-present genotypes have a T-to-G transversion at the fifth base from the 5＇ end of the reverse sY84 primer. These prevalent false positives, which were not only observed in infertile men, but also observed in donors, resulted from a single-nucleotide polymorphism （SNP） named rs72609647 in the targeting sequence of the reverse sY84 primer. Our study suggests that a pre-screening of existence of rs72609647 polymorphism can prevent the frequent false positive results of AZFa microdeletions detection in the infertile Chinese males. Given the SNP rs72609647 was recently found in a deep sequencing of a Chinese individual, the current EAA and EMQN standards may need to be scrutinized among different populations to avoid the potential genetic variations in the primer binding sequences.

关键词： male infertility multiplex polymerase chain reaction rs72609647 single-nucleotide polymorphism sY84 Y-chromosomemicrodeletion

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Optimization of Bartonella henselae multilocus sequence typing scheme using single-nucleotide polymorphism analysis of SOLID sequence data

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Chinese Medical Journal 2012年第13期125卷 2284-2288页

作者： ZHAO Fan Gemma Chaloner Alistair Darby SONG Xiu-ping LI Dong-mei Richard Birtles LIU Qi-yong State Key Laboratory for Infectious Diseases Prevention and Control National Institute for Communicable Disease Control and Prevention Chinese Center for Disease Control and Prevention Beijing 102206 China Department of Epidemiology Beijing Institute of Heart Lung and Blood Vessel Diseases Beijing An Zhen Hospital Capital Medical University Beijing 100029 China National Centre for Zoonosis Research School of Veterinary Science University of Liverpool Cheshire CH64 7TE UK Centre for Genomics Research Biosciences Building University of Liverpool Crown Street Liverpool L69 7ZB UK School of Environment and Life Sciences University of Salford M5 4WT UK

Background Multi-locus sequence typing （MLST） is widely used to explore the population structure of numerous bacterial pathogens. However, for genotypically-restricted pathogens, the sensitivity of MLST is limited by a paucity of variation within selected loci. For Bartonella henselae （B. henselae）, although the MLST scheme currently used has been proven useful in defining the overall population structure of the species, its reliability for the accurate delineation of closely-related sequence types, between which allelic variation is usually limited to, at most, one or two nucleotide polymorphisms. Exploitation of high-throughput sequencing data allows a more informed selection of MLST loci and thus, potentially, a means of enhancing the sensitivity of the schemes they comprise. Methods We carried out SOLID resequencing on 12 representative B. henselae isolates and explored these data using single nucleotide polymorphism （SNP） analysis. We determined the number and distribution of SNPs in the genes targeted by the established MLST scheme and modified the position of loci within these genes to capture as much genetic variation as possible. Results Using genome-wide SNP data, we found the distribution of SNPs within each open reading frame （ORF） of MLST loci, which were not represented by the established B. henselae MLST scheme. We then modified the position of loci in the MLST scheme to better reflect the polymorphism in the ORF as a whole. The use of amended loci in this scheme allowed previously indistinguishable ST1 strains to be differentiated. However, the diversity of B. henselae was still rare in China. Conclusions Our study demonstrates the use of SNP analysis to facilitate the selection of MLST loci to augment the currently-described scheme for B. henselae. And the diversity among B. henselae strains in China is markedly less than that observed in B. henselae populations elsewhere in the world.

关键词： Bartonella henselae multilocus sequence typing single-nucleotide polymorphism

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A narrative review of single-nucleotide polymorphism detection methods and their application in studies of Staphylococcus aureus

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Journal of Bio-X Research 2021年第1期4卷 1-9页

作者： Ying Jian Min Li Department of Laboratory Medicine Shanghai Jiao Tong University School of Medicine Affiliated Renji HospitalShanghaiChina

single-nucleotide polymorphisms(SNPs)are the third generation of genetic markers,having been refined from the first generation of restriction fragment length polymorphisms and the second generation of microsatellite *** represent a focal point of current studies of Staphylococcus *** one hand,this review aims to summarize common methodologies for detecting *** methods have typically included DNA genome sequencing methods and PCR-based detection *** methods,such as mass spectrometry,denaturing high-performance liquid chromatography,SNaPshot,and SNP array have also been employed for SNP *** the other hand,we enumerate a series of applications of SNP analysis in investigations of Staphylococcus *** analysis can be applied to investigate epidemiological outbreaks and transmission of Staphylococcus aureus infections,the transmission and evolution of antimicrobial resistance genes in Staphylococcus aureus isolates,interactions of Staphylococcus aureus with other bacteria,and the links between Staphylococcus aureus in humans and livestock.

关键词： real-time PCR single-nucleotide polymorphism Staphylococcus aureus transmission whole-genome sequencing

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Early prediction of growth patterns after pediatric kidney transplantation based on height-related single-nucleotide polymorphisms

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Chinese Medical Journal 2024年第10期137卷 1199-1206页

作者： Yi Feng Yonghua Feng Mingyao Hu Hongen Xu Zhigang Wang Shicheng Xu Yongchuang Yan Chenghao Feng Zhou Li Guiwen Feng Wenjun Shang Department of Renal Transplantation The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Precision Medicine Center Academy of Medical ScienceZhengzhou UniversityZhengzhouHenan 450052China

Background:Growth retardation is a common complication of chronic kidney disease in children,which can be partially relieved after renal *** study aimed to develop and validate a predictive model for growth patterns of children with end-stage renal disease(ESRD)after kidney transplantation using machine learning algorithms based on genomic and clinical ***:A retrospective cohort of 110 children who received kidney transplants between May 2013 and September 2021 at the First Affiliated Hospital of Zhengzhou University were recruited for whole-exome sequencing(WES),and another 39 children who underwent transplant from October 2021 to March 2022 were enrolled for external *** on previous studies,we comprehensively collected 729 height-related single-nucleotide polymorphisms(SNPs)in exon *** machine learning algorithms and 10-fold cross-validation analysis were employed for model ***:The 110 children were divided into two groups according to change in height-for-age *** univariate analysis,age and 19 SNPs were incorporated into the model and *** random forest model showed the best prediction efficacy with an accuracy of 0.8125 and an area under curve(AUC)of 0.924,and also performed well in the external validation cohort(accuracy,0.7949;AUC,0.796).Conclusions:A model with good performance for predicting post-transplant growth patterns in children based on SNPs and clinical variables was constructed and validated using machine learning *** model is expected to guide clinicians in the management of children after renal transplantation,including the use of growth hormone,glucocorticoid withdrawal,and nutritional supplementation,to alleviate growth retardation in children with ESRD.

关键词： Growth Machine learning Pediatric kidney transplantation single-nucleotide polymorphism

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single-nucleotide polymorphisms and haplotypes of non-coding area in the CP gene are correlated with Parkinson's disease

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Neuroscience Bulletin 2015年第2期31卷 245-256页

作者： Na Zhao Jianqiu Xiao Zhiyong Zheng Guoqiang Fei Feng Zhang Lirong Jin Chunjiu Zhong Department of Neurology Zhongshan Hospital and Shanghai Medical College State Key Laboratory of Medical Neurobiology Institute of Brain Science Fudan University School of Life Sciences Fudan University Xinxiang College of Medicine

Our previous studies have demonstrated that ceruloplasmin （CP） dysmetabolism is correlated with Parkinson＇s disease （PD）. However, the causes of decreased serum CP levels in PD patients remain to be clarified. This study aimed to explore the potential association between genetic variants of the CP gene and PD. Clinical features, serum CP levels, and the CP gene （both promoter and coding regions） were analyzed in 60 PD patients and 50 controls. A luciferase reporter system was used to investigate the function of promoter single-nucleotide polymorphisms （SNPs）. High-density comparative genomic hybridization microarrays were also used to detect large-scale copy-number variations in CP and an additional 47 genes involved in PD and/or copper/ iron metabolism. The frequencies of eight SNPs （one intronic SNP and seven promoter SNPs of the CP gene） and their haplotypes were significantly different between PD patients, especially those with lowered serum CP levels, and controls. However, the luciferase reporter system revealed no significant effect of the risk haplotype on promoter activity of the CP gene. Neither these SNPs nor their haplotypes were correlated with the Hoehn and Yahr staging of PD. The results of this study suggest that common genetic variants of CP are associated with PD and further investigation is needed to explore their functions in PD.

关键词： Parkinson's disease ceruloplasmin single-nucleotide polymorphism haplotype copy-number variation

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single-nucleotide polymorphisms of HLA and Polygonum multiflorum-induced liver injury in the Han Chinese population

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World Journal of Gastroenterology 2020年第12期26卷 1329-1339页

作者： Wan-Na Yang Li-Li Pang Ji-Yuan Zhou Yuan-Wang Qiu Liang Miao Shou-Yun Wang Xiang-Zhong Liu Kang-An Tan Wan-Wan Shi Gui-Qiang Wang Feng-Qin Hou Department of Infectious Diseases Peking University First HospitalBeijing 100034China Department of Gastroenterology and Hematology AEROSPACE 731 HospitalBeijing 100074China Department of Gastroenterology the Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510260Guangdong ProvinceChina Department of Liver Diseases the Wuxi Fifth Affiliated Hospital of Jiangnan UniversityWuxi 214011Jiangsu ProvinceChina Department of Liver Diseases the Third Hospital of QinhuangdaoQinhuangdao 066001Hebei ProvinceChina Department of Liver Diseases Yantai City Hospital for Infectious DiseasesYantai 264001Shandong ProvinceChina Department of Infectious Diseases Peking University International HospitalBeijing 102206China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases Hangzhou 310003Zhejiang ProvinceChina

BACKGROUND Polygonum multiflorum is one of the leading causes of herb-induced liver injury in ***-B*35:01 is reported to be a potential biomarker of Polygonum multiflorum-induced liver injury(PM-DILI).However,little is known about the relationship between single-nucleotide polymorphisms(SNPs) and *** To identify SNPs that indicate susceptibility to PM-DILI METHODS We conducted a systematic study enrolling 382 participants from four independent hospitals,including 73 PM-DILI patients,118 patients with other drug-induced liver injury(other-DILI) and 191 healthy ***-exome sequencing was performed for 8 PM-DILI patients and 8 healthy controls who were randomly selected from the above *** SNPs that showed high frequencies in the 8 PM-DILI patients were selected as candidate SNPs and then screened in 65 PM-DILI patients,118 other-DILI patients and 183 healthy controls using the MassARRAY ***-B high-resolution genotyping was performed for the 73 PM-DILI and 118 other-DILI *** Han-MHC database was selected as a population control for HLA-B analysis.P <6.25 x 103 after Bolferroni correction was considered *** The frequencies of rslll686806 in the HLA-A gene,rs1055348 in the HLA-B gene,and rs202047044 in the HLA-DRB1 gene were significantly higher in the PM-DILI group than in the control group [27.2% vs 11.6%,P=1.72×105,odds ratio(OR)=3.96,95% confidence interval(Cl):2.21-7.14;42.5% vs 8.6%,P=1.72×10-19 OR=13.62,95% CI:7.16-25.9;22.9% vs 8.1%,P=4.64×106,OR=4.1,95% CI:2.25-7.47].Only rs1055348 showed a significantly higher frequency in the PM-DILI group than in the other-DILI group(42.5% vs 13.6%,P=1.84×10-10,OR=10.06,95% Cl:5.06-20.0),which suggested that it is a specific risk factor for ***1055348 may become a tag for HLA-B*35:01 with 100% sensitivity and 97.7% specificity in the PM-DILI group and 100% sensitivity and 98.1% specificity in the other-DILI ***,HLA-B*35:01 was confirmed t

关键词： Drug-induced liver injury Polygonum multiflorum single-nucleotide polymorphism rs111686806 rs1055348 rs202047044 HLA-B*35

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Diabetic kidney disease:Are the reported associations with singlenucleotide polymorphisms disease-specific?

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World Journal of Diabetes 2021年第10期12卷 1765-1777页

作者： Marek Saracyn Bartłomiej Kisiel Maria Franaszczyk Dorota Brodowska-Kania WawrzyniecŻmudzki Robert Małecki Longin Niemczyk Przemysław Dyrla Grzegorz Kamiński RafałPłoski Stanisław Niemczyk Department of Internal Diseases Nephrology and DialysisMilitary Institute of MedicineWarsaw 04-141Poland Department of Endocrinology and Isotope Therapy Military Institute of MedicineWarsaw 04-141Poland Clinical Research Support Center Military Institute of MedicineWarsaw 04-141Poland Department of Medical Biology Molecular Biology LaboratoryInstitute of CardiologyWarsaw 04-628Poland Department of Nephrology Międzyleski Specialist Hospital in WarsawWarsaw 04-749Poland Department of Nephrology Dialysis and Internal DiseasesWarsaw Medical UniversityWarsaw 02-097Poland Department of Gastroenterology Military Institute of MedicineWarsaw 04-141Poland Department of Medical Genetics Medical University of WarsawWarsaw 02-106Poland

BACKGROUND The genetic backgrounds of diabetic kidney disease(DKD)and end-stage kidney disease(ESKD)have not been fully *** To examine the individual and cumulative effects of single-nucleotide polymorphisms(SNPs)previously associated with DKD on the risk for ESKD of diabetic etiology and to determine if any associations observed were specific for *** Fourteen SNPs were genotyped in hemodialyzed 136 patients with diabetic ESKD(DKD group)and 121 patients with non-diabetic ESKD(NDKD group).Patients were also re-classified on the basis of the primary cause of chronic kidney disease(CKD).The distribution of alleles was compared between diabetic and nondiabetic groups as well as between different *** weighted multilocus genetic risk score(GRS)was calculated to estimate the cumulative risk conferred by all *** GRS distribution was then compared between the DKD and NDKD groups as well as in the groups according to the primary cause of *** One SNP(rs841853;SLC2A1)showed a nominal association with DKD(P=0.048;P>0.05 after Bonferroni correction).The GRS was higher in the DKD group(0.615±0.260)than in the NDKD group(0.590±0.253),but the difference was not significant(P=0.46).The analysis of associations between GRS and individual factors did not show any significant ***,the GRS was significantly higher in patients with glomerular disease than in those with tubulointerstitial disease(P=0.014)and in those with a combined group(tubulointerstitial,vascular,and cystic and congenital disease)(P=0.018).CONCLUSION Our results suggest that selected SNPs that were previously associated with DKD may not be specific for DKD and may confer risk for CKD of different etiology,particularly those affecting renal glomeruli.

关键词： Diabetic kidney disease Chronic kidney disease End-stage kidney disease single-nucleotide polymorphism Diabetes mellitus

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Assessing the causality of interferon-γ and its receptor 1/2 with systemic lupus erythematosus risk using genetic data

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Rheumatology & Autoimmunity 2024年第2期4卷 109-118页

作者： Minjing Chang Kaixin Yao Jiawei Hao Yinqi Long Lulin Qiao Yaru Zhang Kexin Ma Peifeng He Shanxi Key Laboratory of Big Data for Clinical Decision Shanxi Medical UniversityTaiyuanShanxiChina Ministry of Education Key Laboratory of Cellular Physiology at Shanxi Medical UniversityTaiyuanShanxiChina Institute of Medical Data Sciences Shanxi Medical UniversityTaiyuanShanxiChina

Background::The interferon-γ (IFN-γ) signaling pathway is activated in systemic lupus erythematosus (SLE). This study aimed to assess the causal association between IFN-γ, IFN-γ receptor 1 (IFN-γR1), and IFN-γR2 and SLE using a bidirectional Mendelian randomization (MR) ***::Genetic instruments for exposure to IFN-γ, IFN-γR1, and IFN-γR2 were derived from a large genome-wide association study (GWAS) that included a sample size of 3301 participants. Instrumental variables for SLE were selected from another independent GWAS analysis comprising 5201 cases and 6099 controls with European ancestry. Bidirectional two-sample MR was performed using inverse variance weighting, MR-Egger regression, and weighted median methods. A series of sensitivity analyses were conducted to assess the robustness of the ***::The inverse variance weighting showed that IFN-γ had a positive causal association with the risk of SLE (odd ratio [OR] = 1.24, 95% confidence interval [CI]: 1.03–1.47, p = 0.018). IFN-γR2 levels were not associated with SLE risk after adjustment for multiple comparisons (OR= 0.85, 95% CI: 0.73–0.99, p= 0.034). No genetic association was also detected between IFN-γR1 and SLE (OR= 0.97, 95% CI: 0.79–1.19, p= 0.768). Evidence from bidirectional MR did not support reverse causality. The weighted median regression also showed directionally similar estimates. Conclusion::Higher levels of IFN-γ are significantly associated with an increased risk of SLE, providing insights into the pathogenesis of SLE.

关键词： interferon-γ interferon-γreceptor Mendelian randomization risk factor single-nucleotide polymorphism systemic lupus erythematosus

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Affection of single-nucleotide polymorphisms in miR-27a, miR-124a, and miR-146a on Susceptibility to Type 2 Diabetes Mellitus in Chinese Han People

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Chinese Medical Journal 2015年第4期128卷 533-539页

作者： Tong-Tong Wang Yong-Jie Chen Lu-Lu Sun Si-Jia Zhang Zhong-Yu Zhou Hong Qiao Department of Endemic Disease The Second Affiliated Hospital Harbin Medical University Harbin Heilongjiang 150081 China Department of Biostatistics Public Health College Harbin Medical University Harbin Heilongjiang 150081 China

Background：polymorphisms of microRNA （miRNA）,as a novel mechanism,are closely associated with disease states by interfering with miRNA *** correlations have been identified between single-nucleotide polymorphisms （SNPs） in miRNA,but the effect on type 2 diabetes mellitus （T2DM） onset among Chinese population remains ***,the aim of this study was to identify correlations between common SNPs in miR-27a,miR-146a,and miR-124a with T2DM among a Chinese population,as well as to explore diabetic pathological mechanisms and the impact of environmental ***：SNPscan technology was used to genotype 995 patients newly diagnosed with T2DM and 967 *** regression analysis was performed to compare mutation frequencies between cases and ***：We found no significant correlations between all genotypes of these miRNAs and T2DM in our ***,stratification analysis identified a lower risk of T2DM associated with the rs531564GC genotype among younger subjects （age ＜ 45 years）（adjusted P =0.043; odds ratio [OR] =0.73; 95％ confidence interval [CI] =0.54-0.99）.Furthermore,the rs895819CC genotype in overweight people （24 ＜ body mass index [BMI] ＜ 28） was significantly associated with an increased risk of T2DM （adjusted P =0.042; OR =1.73; 95％ CI =1.02-2.94）,while the rs2910164 genotype in miR-146a was not significantly correlated with *** genetic risk score was calculated based on the number of risk alleles of the three SNPs and was found to be correlated to total cholesterol （adjusted P =0.021）.Conclusions：The rs531564GC genotype acted as a protective factor to decrease the risk of T2DM in younger subjects （age ＜ 45 years）,while the presence of the rs895819CC genotype increased the risk of illness among overweight subjects （24 ＜ BMI ＜ 28 kg/m2）.The presence of SNPs in miRNA might promote disease by affecting miRNA expression and gene ***,miRNA mimics or inhibitors that directly regulate miRNA expression

关键词： Epigenetics Genetic Variation MicroRNA single-nucleotide polymorphism Type 2 Diabetes Mellitus

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