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1.
Sette A  Sidney J 《Immunogenetics》1999,50(3-4):201-212
 Herein, we review the epitope approach to vaccine development, and discuss how knowledge of HLA supertypes might be used as a tool in the development of such vaccines. After reviewing the main structural features of the A2-, A3-, B7-, and B44- supertype alleles, and biological data demonstrating their immunological relevance, we analyze the frequency at which these supertype alleles are expressed in various ethnicities and discuss the relevance of those observations to vaccine development. Next, the existence of five new supertypes (A1, A24, B27, B58, and B62) is reported. As a result, it is possible to account for the predominance of all known HLA class I with only nine main functional binding specificities. The practical implications of this finding, as well as its relevance to understanding the functional implication of MHC polymorphism in humans, are discussed.  相似文献
2.
中国西北地区汉,回,维,藏民族HLA—DRB基因多态性的研究   总被引:29,自引:2,他引:27  
赖淑苹  任惠民 《遗传学报》1999,26(5):447-457
按照第11届国际相容性抗原研讨会工作会议HLAⅡ类PCR-SSO分型标准和美国国立骨髓供者计划组织对HLA DRB位点等位基因分型要求,设计合成1对引物,扩增HLA DRB DNA片段,长度为256bp,设计合成不同片段大小探针27种,可检出DRB座位上DRB1的39种等位基因,DRB3的3种等位基因,DRB4的1种等位基因和DRB5的34种等位基因。  相似文献
3.
本文是1991年11月6—13日横滨第11届国际组织相容性会议(IHWC)协作科研中我国主要少数民族(苗族、布依族、蒙古族、满族、回族、藏族、维吾尔族)和南北汉族样本HLAⅠ、Ⅱ、Ⅲ类抗原多态性分析的联合报告。聚类分析表明,苗、布依与南方汉族聚类,蒙、满、回、藏与北方汉族集群,提示中华民族包含南北两大群体。维吾尔族非常疏远地共聚于高加索人种。高加索人种起源的HLA抗原基因频率(A3、B8等)由西向东又由北向南递减。东南亚蒙古人种起源的HLA抗原基因频率(B46等)由南向北递减。HLA抗原基因频率的这种梯度分布反映我们祖先自远古史前时期以来的不断迁移和相互融合的过程。本文讨论了中华民族包含南北两大群体这一事实对于中华民族起源的启示。  相似文献
4.
江浙沪地区汉族人群HLA单体型研究   总被引:21,自引:0,他引:21  
利用HLA血清学和分子生物学分型方法对江浙沪地区汉族人群166对夫妻进行HLA-A,B和DR B1单体型调查,并分析HLA单体型的分布特征.结果显示,江浙沪地区汉族人群HLA-A2,A11,A24,B13,B46,B60,DRB104,DRB108,DRB109,DRB112和DRB115有较高的频率分布(>10%).研究中发现HLA-A-B,B-DRB1单体型分别有128条和182条,占理论单体型总数的19.28%(128/664)和27.41%(182/664).其中有18种A-B单体型频率大于0.5%(连锁不平衡参数△>0),有23种B-DRB1单体型频率大于0.5%(△>0).A-B-DRB1单体型有351条,占理论单体型总数的52.86%(351/664),其中8种单体型频率大于0.5%(△>0),A 30-B13-DRB107(4.22 %),A2-B46-DRB109(3.77%),A33-B58-DRB117(3.01%),A33-B58-DRB113.1(1.81%)和A11-B75-DRB112(1.51%)是最常见单体型.江浙沪地区汉族人群HLA单体型有其自身分布特点,遗传特征介于南北汉族之间,在东亚人群中中国汉族群体HLA多态性较为丰富.  相似文献
5.
寡核苷酸DNA Microarray用于HLA DRB1基因分型的研究   总被引:18,自引:1,他引:17  
对寡核苷酸DNA Microarray用于HLA DRB1基因分型的技术进行研究。常规的酚/氯仿法提取标准血样基因组DNA,在DRB1的exon2区域设计一对引物,经PCR扩增基因组相应区段并用Cy5-dCTP进行标记。设计寡核苷酸分型探针,将探针固定在APS-PDC法制作的DNA Microarray上,用标记的PCR产物与之杂交,扫描仪对杂交效果进行扫描,Imagene软件对杂交图像进行分析。共检测了33例标准血样的HLA DRB1基因型。检测结果证明研制的DNA Microarray准确、灵敏。DNA Microarray技术可以有效地检测DRB1等位基因,对比常规的PCR-SSP和PCR-SSO方法、分型基因芯片方法更为直观,并有集成化优势。  相似文献
6.
Pathogen resistance and genetic variation at MHC loci   总被引:14,自引:0,他引:14  
Abstract.— Balancing selection in the form of heterozygote advantage, frequency-dependent selection, or selection that varies in time and/or space, has been proposed to explain the high variation at major histocompatibility complex (MHC) genes. Here the effect of variation of the presence and absence of pathogens over time on genetic variation at multiallelic loci is examined. In the basic model, resistance to each pathogen is conferred by a given allele, and this allele is assumed to be dominant. Given that s is the selective disadvantage for homozygotes (and heterozygotes) without the resistance allele and the proportion of generations, which a pathogen is present, is e , fitnesses for homozygotes become (1 — s )(n-1)e and the fitnesses for heterozygotes become (1 — s )(n-2)e, where n is the number of alleles. In this situation, the conditions for a stable, multiallelic polymorphism are met even though there is no intrinsic heterozygote advantage. The distribution of allele frequencies and consequently heterozygosity are a function of the autocorrelation of the presence of the pathogen in subsequent generations. When there is a positive autocorrelation over generations, the observed heterozygosity is reduced. In addition, the effects of lower levels of selection and dominance and the influence of genetic drift were examined. These effects were compared to the observed heterozygosity for two MHC genes in several South American Indian samples. Overall, resistance conferred by specific alleles to temporally variable pathogens may contribute to the observed polymorphism at MHC genes and other similar host defense loci.  相似文献
7.
PCR-SSP技术对广东汉族人HLA-DR基因分型   总被引:13,自引:0,他引:13       下载免费PDF全文
 探索具有高分辨率、高特异性和简捷快速的方法对HLA-DR基因分型,为临床器官移植配型和疾病相关性分析提供实用的方法和基础资料.利用DR1~DRw18序列特异性的19组引物及1对内参照引物进行PCR扩增即PCR-SSP对HLA-DR进行基因分型,扩增产物经琼脂糖凝胶电泳,溴乙锭染色,在紫外光下观察分型结果.每个被检个体的DR型别可由特异引物扩增出现的电泳谱带直接判断.双盲检测22例的结果100%正确.在102例中国广东地区汉族人中,DR9和DR2的基因频率最高,分别为0.2205和0.1912,DR10为最低(0.0098).与用PCR-SSO方法分型获得的结果比较,基因型别分布基本一致,但一些等位基因的频率有差异,表明HLA-DR基因频率的分布在不同地区、不同种族的人群间存在着差异.PCR-SSP法分辨率和特异性虽不及PCR-SSO法但比血清学方法精细,分型的全过程只需2~4h能满足临床器官移植配型的要求.基因频率调查结果为器官移植配型和疾病相关性分析提供了基础资料.  相似文献
8.
Peptide binding motifs and specificities for HLA-DQ molecules   总被引:13,自引:0,他引:13  
 HLA-DQ molecules have been associated with susceptibility to a number of autoimmune and other diseases, possibly through the peptide repertoire that can be presented by different allelic products. It is thus of importance to understand which peptides can be bound by different HLA-DQ allelic products. Recently, a model for HLA-DQ has been described and used to derive peptide positional environments for HLA-DQ allelic products. By combining the peptide positional environments with known HLA-DQ peptide binding motifs, a set of predictions of likely anchor motifs for many of the products of HLA-DQ allelic variants are made and presented in a table referred to as a roadmap for HLA-DQ peptide binding specificities. Received: 3 March 1999 / Revised: 20 May 1999  相似文献
9.
Ossification of the posterior longitudinal ligament of the spine (OPLL) is recognized as a common disorder among Japanese and throughout Asia. Estimates of its prevalence are in the range of 1. 9%-4.3%. Although its etiology is thought to involve a multiplicity of factors, epidemiological and family studies strongly implicate genetic susceptibility in the pathogenesis of OPLL. In this study we report an identification of a predisposing locus for OPLL, on chromosome 6p, close to the HLA complex. The evidence for this localization is provided by a genetic-linkage study of 91 affected sib pairs from 53 Japanese families. In this sib-pair study, D6S276, a marker lying close to the HLA complex, gives evidence for strongly significant linkage (P = .000006) to the OPLL locus. A candidate gene in the region, that for collagen 11A2, was analyzed for the presence of molecular variants in affected probands. Of 19 distinct variants identified, 4 showed strong statistical associations with OPLL (highest P = .0004). These observations of linkage and association, taken together, show that a genetic locus for OPLL lies close to the HLA region, on chromosome 6p.  相似文献
10.
Killer immunoglobulin-like receptors (KIRs) regulate the activity of NK and T cells through interaction with specific HLA class I molecules on target cells. To date, 16 KIR genes and pseudogenes have been identified. Diversity in KIR gene content and KIR allelic and haplotype polymorphism has been observed between different ethnic groups. Here, we present data on the KIR gene distribution in Pacific Islands populations. Sixteen KIR genes were observed in Pacific Islands populations from the Cook Islands, Samoa, Tokelau, and Tonga. The majority of KIR genes were present at similar frequencies between the four populations with KIR2DL4, KIR3DL2, and KIR3DP1 genes observed in all individuals. Commonly observed KIR genes in Pacific Islands populations (pooled frequencies) were KIR2DL1 (0.77), KIR2DL3 (0.77), KIR3DL1 (0.65), KIR3DL3 (0.93), KIR2DS4/1D (0.78), and KIR2DP1 (0.82), compared to the less-frequently observed KIR2DL2 (0.27), KIR2DL5 (0.30), KIR2DS1 (0.19), KIR2DS2 (0.27), KIR2DS3 (0.16), KIR2DS5 (0.17), and KIR3DS1 (0.18) genes. Differences in KIR gene frequency distributions were observed between the Pacific Islands populations and when compared to other populations. Sixty-nine different genotypes were identified, with five genotypes accounting for more then 50% of all genotypes observed. The number of genotypes observed in each population was similar in the Cook Islands, Samoan, and Tokelauan populations (19, 18, and 19, respectively), but 26 different genotypes were observed in Tongans. The putative haplotype A was predominantly observed over haplotype B in all Pacific Islands populations. Significant linkage disequilibrium was observed for a number of KIR gene pairs.  相似文献
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