全文获取类型
收费全文 | 10942篇 |
免费 | 832篇 |
国内免费 | 86篇 |
学科分类
生物科学 | 11860篇 |
出版年
2023年 | 61篇 |
2022年 | 130篇 |
2021年 | 208篇 |
2020年 | 131篇 |
2019年 | 172篇 |
2018年 | 178篇 |
2017年 | 186篇 |
2016年 | 290篇 |
2015年 | 508篇 |
2014年 | 584篇 |
2013年 | 639篇 |
2012年 | 942篇 |
2011年 | 894篇 |
2010年 | 565篇 |
2009年 | 507篇 |
2008年 | 711篇 |
2007年 | 637篇 |
2006年 | 582篇 |
2005年 | 495篇 |
2004年 | 495篇 |
2003年 | 441篇 |
2002年 | 422篇 |
2001年 | 135篇 |
2000年 | 126篇 |
1999年 | 116篇 |
1998年 | 118篇 |
1997年 | 79篇 |
1996年 | 76篇 |
1995年 | 64篇 |
1994年 | 69篇 |
1993年 | 73篇 |
1992年 | 68篇 |
1991年 | 68篇 |
1990年 | 70篇 |
1989年 | 85篇 |
1988年 | 58篇 |
1987年 | 80篇 |
1986年 | 63篇 |
1985年 | 46篇 |
1984年 | 56篇 |
1983年 | 46篇 |
1982年 | 42篇 |
1981年 | 35篇 |
1980年 | 28篇 |
1979年 | 31篇 |
1978年 | 30篇 |
1977年 | 31篇 |
1976年 | 40篇 |
1974年 | 28篇 |
1972年 | 30篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
Amélie Faubert Angela Samaan Jacques Thibodeau 《The Journal of biological chemistry》2002,277(4):2750-2755
In the endocytic pathway of antigen-presenting cells, HLA-DM catalyzes the exchange between class II-associated invariant chain peptide (CLIP) and antigenic peptides onto major histocompatibility complex class II molecules. At low pH of lysosomal compartments, both HLA-DM and HLA-DR undergo conformational changes, and it was recently postulated that two partially exposed tryptophans on HLA-DM might be involved in the interaction between the two molecules. To define contact regions on HLA-DM, we have conducted site-directed mutagenesis on those two hydrophobic residues. The HLA-DM alphaW62A,betaW120A (DM(W62A/W120A)) double mutant was expressed in HLA-DR(+) HeLa cells expressing invariant chain, and the activity of this DM molecule was assessed. Flow cytometry analysis of cell surface DR-CLIP complexes revealed that DM(W62A/W120A) removes CLIP as efficiently as its wild-type counterpart. DM(W62A/W120A) was found in the endocytic pathway by immunofluorescence, and DM-DR complexes were immunoprecipitated from these cells at pH 5. Finally, mutations alphaW62A and betaW120A on HLA-DM did not affect the association with HLA-DO. The complex egresses the endoplasmic reticulum and accumulates in endocytic vesicles. Moreover, DO and DM(W62A/)W120A were co-immunoprecipitated at pH 7. We conclude that the alpha62 and beta120 tryptophan residues are not required for the activity of DM, nor are they directly implicated in the interaction with DR or DO. 相似文献
2.
3.
Summary A male fetus of a pregnancy known to be at risk for X-linked mental retardation with fragile site Xq27 was found to be affected by demonstrating the marker X-chromosome in five of 180 (2.8%) of metaphases derived from amniocytes cultured in medium 199. The results were confirmed in fetal lymphocytes (25 of 86 metaphases, i.e. 29%), and fetal fibroblasts (five of 100 metaphases when cultured in medium 199, and 14 of 100 after exposure to methotrexate for 43 h).This work was supported in part by a research grant from the Deutsche Forschungsgemeinschaft 相似文献
4.
5.
6.
7.
8.
In vivo neutralization of TNF-alpha promotes humoral autoimmunity by preventing the induction of CTL. 总被引:3,自引:0,他引:3
C S Via A Shustov V Rus T Lang P Nguyen F D Finkelman 《Journal of immunology (Baltimore, Md. : 1950)》2001,167(12):6821-6826
Neutralization of TNF-alpha in humans with rheumatoid arthritis or Crohn's disease has been associated with the development of humoral autoimmunity. To determine the effect of TNF-alpha neutralization on cell-mediated and humoral-mediated responses, we administered anti-TNF-alpha mAb to mice undergoing acute graft-vs-host disease (GVHD) using the parent-into-F(1) model. In vivo neutralization of TNF-alpha blocked the lymphocytopenic features characteristic of acute GVHD and induced a lupus-like chronic GVHD phenotype (lymphoproliferation and autoantibody production). These effects resulted from complete inhibition of detectable antihost CTL activity and required the presence of anti-TNF-alpha mAb for the first 4 days after parental cell transfer, indicating that TNF-alpha plays a critical role in the induction of CTL. Moreover, an in vivo blockade of TNF-alpha preferentially inhibited the production of IFN-gamma and blocked IFN-gamma-dependent up-regulation of Fas; however, cytokines such as IL-10, IL-6, or IL-4 were not inhibited. These results suggest that a therapeutic TNF-alpha blockade may promote humoral autoimmunity by selectively inhibiting the induction of a CTL response that would normally suppress autoreactive B cells. 相似文献
9.
10.