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Classifying genotype F of hepatitis B virus into F1 and F2 subtypes

World Journal of Gastroenterology 2005年第40期11卷 6295-6304页

作者： Hideaki Kato Kei Fujiwara Robert G. Gish Hiroshi Sakugawa Hiroshi Yoshizawa Fuminaka Sugauchi Etsuro Orito Ryuzo Ueda Yasuhito Tanaka Takanobu Kato Yuzo Miyakawa Masashi Mizokami Department of Internal Medicine and Molecular Science Hepatology and Gastroenterology First Department of Medicine Department of epidemiology and Control of Infectious Diseases Department of Clinical Molecular Informative Medicine Miyakawa Memorial research Foundation

AIM： To explore the propriety of providing hepatitis B virus （HBV） genotypes F and H with two distinct genotypes. METHODS： Eleven HBV isolates of genotype F （HBV/F） were recovered from patients living in San Francisco, Japan, Panama, and Venezuela, and their full-length sequences were determined. Phylogenetic analysis was carded out among them along with HBV isolates previously reported. RESULTS： Seven of them clustered with reported HBV/F Isolates in the phylogenetic tree constructed on the entire genomic sequence. The remaining four flocked on another branch along with three HBV isolates formerly reported as genotype H. These seven HBV isolates, including the four in this study and the three reported, had a sequence divergence of 7.3-9.5% from the other HBV/F isolates, and differed by 〉13.7% from HBV isolates of the other six genotypes （A-E and G）. Based on a marked genomic divergence, falling just short of 〉8% separating the seven genotypes, these seven HBV/F isolates were classified into F2 subtype and the former seven into F1 subtype provisionally. In a pairwise comparison of the S-gene sequences among the 7 HBV/F2 isolates and against 47 HBV/F1 isolates as well as 136 representing the other six genotypes （A-E and G）, two clusters separated by distinct genetic distances ***： Based on these analyses, dassifying HBV/ F isolates into two subtypes （F1 and F2） would be more appropriate than providing them with two distinct genotypes （F and H）.

关键词： Genotypes Hepatitis B virus Phylogeneticanalysis Subtypes

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A genome-wide scan for pleiotropy between bone mineral density and nonbone phenotypes

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Bone research 2020年第3期8卷 356-364页

作者： Maria A.Christou Georgios Ntritsos Georgios Markozannes Fotis Koskeridis Spyros N.Nikas David Karasik Douglas P.Kiel Evangelos Evangelou Evangelia E.Ntzani Department of Hygiene and epidemiology Clinical and Molecular Epidemiology UnitSchool of MedicineUniversity of loanninaloanninaGreece Department of Medicine Beth Israel Deaconess Medical CenterHarvard Medical SchoolHinda and Arthur Marcus Institute for Aging ResearchHebrew SeniorLifeand the Broad Institute of MIT&HarvardCambridgeMAUSA Azrieli Faculty of Medicine Bar llan UniversitySafedIsrael Department of epidemiology and Biostatistics Imperial College LondonLondonUK Department of Health Services Policy and PracticeCenter for Research Synthesis in HealthSchool of Public HealthBrown UniversityProvidenceRlUSA

Osteoporosis is the most common metabolic bone disorder globally and is characterized by skeletal fragility and microarchitectural *** pleiotropy occurs when a single genetic element is associated with more than one *** aimed to identify pleiotropic loci associated with bone mineral density(BMD)and nonbone phenotypes in genome-wide association *** the discovery stage,the NHGRI-EBI Catalog was searched for genome-wide significant associations(P valuegenetic associations of this set of SNPs with femoral neck(FN)and lumbar spine(LS)BMD data from the GEFOS *** variants were claimed at a false discovery rategenetic markers was performed among more than 400000 UK Biobank participants of European ancestry with available genetic and heel bone ultrasound *** the discovery stage,72 BMD-related pleiotropic SNPs were identified,and 12 SNPs located in 11 loci on 8 chromosomes were replicated in the UK *** SNPs were associated,in addition to BMD,with 14 different *** pleiotropic associations were exhibited by rs479844(AP5B1,O V O L 1 genes),which was associated with dermatological and allergic diseases,and rs4072037(M U C 1 gene),which was associated with magnesium levels and gastroenterological *** conclusion,12 BMD-related genome-wide significant SNPs showed pleiotropy with nonbone *** associations can deepen the genetic understanding of bone-related diseases by identifying shared biological mechanisms with other diseases or traits.

关键词： magnesium globally Replication

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Re-evaluation of ABO gene polymorphisms detected in a genomewide association study and risk of pancreatic ductal adenocarcinoma in a Chinese population

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Chinese Journal of Cancer 2014年第2期33卷 68-73页

作者： Hong-Li Xu Jia-Rong Cheng Wei Zhang Jing Wang Herbert Yu Quan-Xing Ni Harvey A.Risch Yu-Tang Gao Department of epidemiology Shanghai Cancer InstituteRenji Hospital Shanghai Jiaotong University School of Medicine epidemiology Program University of Hawaii Cancer Center Department of Surgery Hua Shan Hospital Fudan University Department of epidemiology and Public Health Yale University School of Public Health and Yale Cancer Center

Pancreatic cancer is a fatal malignancy with an increasing incidence in Shanghai, China. A genomewide association study(GWAS) and other work have shown that ABO alleles are associated with pancreatic cancer risk. We conducted a population-based case-control study involving 256 patients with pathologically confirmed pancreatic ductal adenocarcinoma(PDAC) and 548 healthy controls in Shanghai, China, to assess the relationships between GWAS-identified ABO alleles and risk of PDAC. Carriers of the C allele of rs505922 had an increased cancer risk [adjusted odds ratio(OR) = 1.42, 95% confidence interval(CI): 1.02-1.98] compared to TT carriers. The T alleles of rs495828 and rs657152 were also significantly associated with an elevated cancer risk(adjusted OR = 1.58, 95% CI: 1.17-2.14; adjusted OR = 1.51, 95% CI: 1.09-2.10). The rs630014 variant was not associated with risk. We did not find any significant gene-environment interaction with cancer risk using a multifactor dimensionality reduction(MDR) method. Haplotype analysis also showed that the haplotype CTTC was associated with an increased risk of PDAC(adjusted OR = 1.46, 95% CI: 1.12-1.91) compared with haplotype TGGT. GWAS-identified ABO variants are thus also associated with risk of PDAC in the Chinese population.

关键词：中国人群基因多态性全基因组胰腺癌风险关联导管评估

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Relationships between cell cycle pathway gene polymorphisms and risk of hepatocellular carcinoma

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World Journal of Gastroenterology 2016年第24期22卷 5558-5567页

作者： Yue-Li Nan Yan-Ling Hu Zhi-Ke Liu Fang-Fang Duan Yang Xu Shu Li Ting Li Da-Fang Chen Xiao-Yun Zeng Department of epidemiology School of Public Health Guangxi Medical University Medical Scientific research Centre Guangxi Medical University Department of epidemiology and Biostatistics School of Public Health Peking University Health Science Center Key Laboratory of High-Incidence-Tumor Prevention and Treatment (Guangxi Medical University) Ministry of Education

AIM: To investigate the associations between the polymorphisms of cell cycle pathway genes and the risk of hepatocellular carcinoma(HCC). METHODS: We enrolled 1127 cases newly diagnosed with HCC from the Tumor Hospital of Guangxi Medical University and 1200 non-tumor patients from the First Affiliated Hospital of Guangxi Medical University. General demographic characteristics, behavioral information, and hematological indices were collected by unified questionnaires. Genomic DNA was isolatedfrom peripheral venous blood using Phenol-Chloroform. The genotyping was performed using the Sequenom Mass ARRAY i PLEX genotyping method. The association between genetic polymorphisms and risk of HCC was shown by P-value and the odd ratio(OR) with 95% confidence interval(CI) using the unconditional logistic regression after adjusting for age, sex, nationality, smoking, drinking, family history of HCC, and hepatitis B virus(HBV) infection. Moreover, stratified analysis was conducted on the basis of the status of HBV infection, smoking, and alcohol ***: The HCC risk was lower in patients with the MCM4 rs2305952 CC(OR = 0.22, 95%CI: 0.08-0.63, P = 0.01) and with the CHEK1 rs515255 TC, TT, TC/TT(OR = 0.73, 95%CI: 0.56-0.96, P = 0.02; OR = 0.67, 95%CI: 0.46-0.97, P = 0.04; OR = 0.72, 95%CI: 0.56-0.92, P = 0.01, respectively). Conversely, the HCC risk was higher in patients with the KAT2 B rs17006625 GG(OR = 1.64, 95%CI: 1.01-2.64, P = 0.04). In addition, the risk was markedly lower for those who were carriers of MCM4 rs2305952 CC and were also HBs Ag-positive and non-drinking and nonsmoking(P < 0.05, respectively) and for those who were carriers of CHEK1 rs515255 TC, TT, TC/TT and were also HBs Ag-negative and non-drinking(P < 0.05, respectively). Moreover, the risk was higher for those who were carriers of KAT2 B rs17006625 GG and were also HBs Ag-negative(P < 0.05).CONCLUSION: Of 12 cell cycle pathway genes, MCM4, CHEK1 and KAT2 B polymorphisms may be associated with t

关键词： Cell cycle pathway genes Hepatocellular carcinoma Single nucleotide polymorphism Case-control study genetic susceptibility

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Short communication: genetic variations of SLC2A9 in relation to Parkinson’s disease

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Translational Neurodegeneration 2013年第1期2卷 26-29页

作者： Jianjun Gao Hong Xu Xuemei Huang Honglei Chen epidemiology branch National Institute of Environmental Health SciencesResearch Triangle ParkNorth CarolinaUSA Molecular genetics Core Facility National Institute of Environmental Health SciencesResearch Triangle ParkNorth CarolinaUSA Department of Neurology Pennsylvania State University-Milton S.Hershey Medical CenterHersheyPennsylvaniaUSA

Background:Epidemiological studies showed that higher plasma urate was associated with lower risk for Parkinson’s disease(PD)and slower disease *** genome-wide association studies(GWAS)consistently showed that several single nucleotide polymorphisms(SNPs)in the solute carrier family 2 member 9 gene(SLC2A9)were associated with plasma urate concentration and the risk of ***:We conducted a case–control study to examine twelve tag SNPs of the SLC2A9 gene in relation to PD among 788 cases and 911 controls of European *** ratios(OR)and 95%confidence intervals(CI)were derived from logistic regression models,adjusting for age,sex,smoking and caffeine ***:These SNPs were all in linkage disequilibrium(R^(2)>0.7).None of them were associated with PD *** women,however,there was a suggestion that the presence of the minor allele of one SNP(rs7442295)was related to a small increase in PD risk[OR(95%CI)=1.48(1.01-2.16)].Conclusion:This study provides little support for genetic variations of SLC2A9 and PD risk.

关键词： SLC2A9 relation linkage

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Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma

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Frontiers of Medicine 2021年第2期15卷 275-291页

作者： Na Qin Yuancheng Li Cheng Wang Meng Zhu Juncheng Dai Tongtong Hong Demetrius Albanes Stephen Lam Adonina Tardon Chu Chen Gary Goodman Stig EBojesen Maria Teresa Landi Mattias Johansson Angela Risch H-Erich Wichmann Heike Bickeboller Gadi Rennert Susanne Arnold Paul Brennan John KField Sanjay Shete Loic Le Marchand Olle Melander Hans Brunnstrom Geoffrey Liu Rayjean JHung Angeline Andrew Lambertus AKiemeney Shan Zienolddiny Kjell Grankvist Mikael Johansson Neil Caporaso Penella Woll Philip Lazarus Matthew BSchabath Melinda CAldrich Victoria LStevens Guangfu Jin David CChristiani Zhibin Hu Christopher IAmos Hongxia Ma Hongbing Shen Department of epidemiology Center for Global HealthSchool of Public HealthNanjing Medical UniversityNanjing 211166China State Key Laboratory of Reproductive Medicine Center for Global HealthNanjing Medical UniversityNanjing 211166China Department of Bioinformatics School of Biomedical Engineering and InformaticsNanjing Medical UniversityNanjing 211166China Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer MedicineNanjing Medical UniversityNanjing 211166China China International Cooperation Center for Environment and Human Health School of Public HealthNanjing Medical UniversityNanjing 211166China Division of Cancer epidemiology and genetics National Cancer InstituteBethesdaMD 20892-9304USA Department of Integrative Oncology British Columbia Cancer AgencyVancouverBC V5Z 1L3Canada Faculty of Medicine University of Oviedo and CIBERESPOviedo 33006Spain Program in epidemiology Public Health Sciences DivisionFred Hutchinson Cancer Research CenterSeattleWA 98109-1024USA Public Health Sciences Division Swedish Cancer InstituteSeattleWA 98026USA Department of Clinical Biochemistry Copenhagen University HospitalCopenhagen DK-1017Denmark National Cancer Institute BethesdaMD 20892-9304USA genetic epidemiology Group International Agency for Research on CancerLyon 69372France Cancer Center Cluster Salzburg at PLUS Department of Molecular BiologyUniversity of SalzburgHeidelberg 5020Austria Institute of Medical Informatics Biometry and EpidemiologyChair of EpidemiologyLudwig Maximilians UniversityMunichBavaria 80539Germany Department of genetic epidemiology University Medical Center GoettingenGoettingen 37075Germany Technion Faculty of Medicine Carmel Medical CenterHaifa 3448516Israel Markey Cancer Center University of KentuckyLexingtonKY 40506-0054USA Department of Molecular and Clinical Cancer Medicine Roy Castle Lung Cancer Research ProgrammeThe University of Liverpool Institute of Translational MedicineLiverpool L697Z

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely *** integrating a large-scale genotype data of 15581 lung adenocarcinoma(AD)cases,8350 squamous cell carcinoma(SqCC)cases,and 27355 controls,as well as multiple transcriptome and epigenomic databases,we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility *** identified 3064 credible risk variants for NSCLC,which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive *** factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was *** annotation and genebased analysis implicated 894 target genes,including 274 specifics for AD and 123 for SqCC,which were overrepresented in somatic driver genes(ER=1.95,P=0.005).Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways,while SqCC genes were homologous recombination deficiency *** results illustrate the molecular basis of both wellstudied and new susceptibility loci of NSCLC,providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.

关键词： lung cancer genome-wide association study function annotation immune homologous recombination repair deficiency genetic heterogeneity

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Association of a single nucleotide polymorphism at 6q25.1, rs2046210, with endometrial cancer risk among Chinese women

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Chinese Journal of Cancer 2011年第2期30卷 138-143页

作者： Guoliang Li Yong-Bing Xiang Regina Courtney Jia-Rong Cheng Bo Huang Ji-Rong Long Hui Cai Wei Zheng Xiao-Ou Shu Qiuyin Cai Division of epidemiology and Vanderbilt epidemiology Center Department of Medicine Vanderbilt University School of Medicine and Vanderbilt-lngram Cancer Center Nashville Tennessee 37232 USA Department of epidemiology Shanghai Cancer Institute Shanghai 200032 P. R. China.

A recent genome-wide association study identified a new susceptibility locus for breast cancer, rs2046210, which is a single nucleotide polymorphism (SNP) located upstream of the estrogen receptor α (ESR1) gene on chromosome 6q25.1. Given that endometrial cancer shares many risk factors with breast cancer and both are related to estrogen exposure and that rs2046210 is in close proximity to the ESR1 gene, we evaluated the association of SNP rs2046210 with endometrial cancer risk among 953 cases and 947 controls in a population-based, case-control study conducted in Shanghai, China. Logistic regression models were used to derive odds ratios (ORs) and 95% confidence intervals (95% CIs) after adjusting for potential confounders. We found that the A allele of rs2046210, linked to an increased risk of breast cancer, was associated with increased but not statistically significant risk of endometrial cancer (OR = 1.16, 95% CI = 0.96-1.41 for the GA and AA genotypes compared with the GG genotype); the association was stronger among post-menopausal women (OR = 1.28, 95% CI = 1.00-1.65). The association tended to be stronger among women with higher or longer estrogen exposure than among women with relatively lower or shorter exposure to estrogen. Our study suggests that rs2046210 may play a role in the etiology of endometrial cancer. Additional studies are needed to confirm our findings.

关键词：单核苷酸多态性子宫内膜癌风险因素协会妇女 Logistic回归模型中国雌激素受体

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East meets West: ethnic differences in prostate cancer epidemiology between East Asians and Caucasians

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Chinese Journal of Cancer 2012年第9期31卷 421-429页

作者： Tomomi Kimura epidemiology Janssen Pharmaceutical K.K.Tokyo 101-0065Japan

Prostate cancer is the most prevalent cancer in males in Western countries. The reported incidence in Asia is much lower than that in African Americans and European Caucasians. Although the lack of systematic prostate cancer screening system in Asian countries explains part of the difference, this alone cannot fully explain the lower incidence in Asian immigrants in the United States and west-European countries compared to the black and non-Hispanic white in those countries, nor the somewhat better prognosis in Asian immigrants with prostate cancer in the United States. Soy food consumption, more popular in Asian populations, is associated with a 25% to 30% reduced risk of prostate cancer. Prostate- specific antigen (PSA) is the only established and routinely implemented clinical biomarker for prostate cancer detection and disease status. Other biomarkers, such as urinary prostate cancer antigen 3 RNA, may increase accuracy of prostate cancer screening compared to PSA alone. Several susceptible loci have been identified in genetic linkage analyses in populations of countries in the West, and approximately 30 genetic polymorphisms have been reported to modestly increase the prostate cancer risk in genome- wide association studies. Most of the identified polymorphisms are reproducible regardless of ethnicity. Somatic mutations in the genomes of prostate tumors have been repeatedly reported to include deletion and gain of the 8p and 8q chromosomal regions, respectively; epigenetic gene silencing of glutathione Stransferase Pi (GSTP1); as well as mutations in androgen receptor gene. However, the molecular mechanisms underlying carcinogenesis, aggressiveness, and prognosis of prostate cancer remain largely unknown. Gene-gene and/or gene-environment interactions still need to be learned. In this review, the differences in PSA screening practice, reported incidence and prognosis of prostate cancer, and genetic factors between the populations in East and West factors are di

关键词：前列腺癌西方国家种族差异亚洲人流行病学谷胱甘肽-S-转移酶高加索特异性抗原

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genetic and environmental risk factors for primary open-angle glaucoma

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Chinese Medical Journal 2004年第5期117卷 706-710页

作者：范宝剑梁旭辉汪宁林顺潮刘瑶谭霭仙彭智培 Department of Ophthalmology & Visual Sciences Department of epidemiology & Biostatistics Department of Ophthalmology

Background Primary open-angle glaucoma (POAG) is characterized by optic nerve damage and consists of a group of genetically heterogeneous disorders. This study was to investigate the associations of genetic and environmental factors with POAG in a hospital-based Chinese population Methods Thirty-two adult onset POAG patients and 96 age-sex matched control subjects were studied by multivariable logistic regression analysis for the relationships between POAG and its risk factors including family history, diabetes, hypertension, cardiovascular diseases, cigarette smoking, alcohol consumption and polymorphisms of the myocilin and the optineurin genes Results Univariate analysis showed that POAG was related to family history, cardiovascular disease, alcohol consumption and a myocilin sequence alteration (T353I) ( P <0 04) Multivariable logistic regression analysis confirmed that POAG was significantly associated with family history ( OR =20 2), hypertension ( OR =3 58), cigarette smoking ( OR =10 8), alcohol consumption ( OR =0 028) and T353I ( OR =6 03, all P <0 05) Conclusions Family history, hypertension, cigarette smoking and T353I in the myocilin gene are risk factors for POAG Alcohol consumption, however, has a protective effect

关键词： glaucoma open-angle · risk factors · genes

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Serum bile acid profiling reflects enterohepatic detoxification state and intestinal barrier function in inflammatory bowel disease

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World Journal of Gastroenterology 2009年第25期15卷 3134-3141页

作者： Carsten Gnewuch Gerhard Liebisch Thomas Langmann Benjamin Dieplinger Thomas Mueller Meinhard Haltmayer Hans Dieplinger Alexandra Zahn Wolfgang Stremmel Gerhard Rogler Gerd Schmitz Institute of Clinical Chemistry and Laboratory Medicine Regensburg University Medical Center Institute of Human genetics University of Regensburg Department of Laboratory Medicine Konventhospital Barmherzige Brueder Linz Division of genetic epidemiology Department of Medical GeneticsClinical and Molecular PharmacologyInnsbruck Medical University Department of Gastro-enterology University Hospital Heidelberg Department of Internal Medicine I Regensburg University Medical Center

AIM： To determine free and conjugated serum bile acid （BA） levels in inflammatory bowel disease （IBD） subgroups with defined clinical manifestations. METHODS： Comprehensive serum BA profiling was performed in 358 IBD patients and 310 healthy con- trols by liquid chromatography coupled to electrospray ionization tandem mass spectrometry. RESULTS： Serum levels of hyodeoxycholic acid, the CYP3A4-mediated detoxification product of the second- ary BA lithocholic acid （LCA）, was increased significantly in Crohn＇s disease （CD） and ulcerative colitis （UC）, while most other serum BA species were decreased signifi- cantly. Total BA, total BA conjugate, and total BA glyco- conjugate levels were decreased only in CD, whereas total unconjugated BA levels were decreased only in UC. In UC patients with hepatobiliary manifestations, the conjugated primary BAs glycocholic acid, taurocholic acid, and glycochenodeoxycholic acid were as signifi- cantly increased as the secondary BAs LCA, ursodeoxy- cholic acid, and tauroursodeoxycholic acid compared to UC patients without hepatobiliary manifestations. Finally, we found that in ileocecal resected CD patients, the unconjugated primary BAs, cholic acid and chenode- oxycholic acid, were increased significantly compared to controls and patients without surgical interventions. CONCLUSION： Serum BA profiling in IBD patients that indicates impaired intestinal barrier function and increased detoxification is suitable for advanced diag- nostic characterization and differentiation of IBD sub- groups with defined clinical manifestations.

关键词： Bile acids Liquid chromatography Tandem mass spectrometry Inflammatory bowel disease Crohn's disease Ulcerative colitis

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