全文获取类型
收费全文 | 197276篇 |
免费 | 7826篇 |
国内免费 | 905篇 |
专业分类
206007篇 |
出版年
2023年 | 605篇 |
2022年 | 496篇 |
2021年 | 1104篇 |
2020年 | 985篇 |
2019年 | 1019篇 |
2018年 | 13617篇 |
2017年 | 12287篇 |
2016年 | 10282篇 |
2015年 | 5521篇 |
2014年 | 5309篇 |
2013年 | 7050篇 |
2012年 | 12225篇 |
2011年 | 19743篇 |
2010年 | 16180篇 |
2009年 | 11386篇 |
2008年 | 15457篇 |
2007年 | 16882篇 |
2006年 | 5952篇 |
2005年 | 5853篇 |
2004年 | 5954篇 |
2003年 | 5631篇 |
2002年 | 5028篇 |
2001年 | 2457篇 |
2000年 | 2322篇 |
1999年 | 1907篇 |
1998年 | 840篇 |
1997年 | 643篇 |
1996年 | 555篇 |
1995年 | 570篇 |
1994年 | 577篇 |
1993年 | 476篇 |
1992年 | 1298篇 |
1991年 | 1231篇 |
1990年 | 1060篇 |
1989年 | 990篇 |
1988年 | 937篇 |
1987年 | 790篇 |
1986年 | 705篇 |
1985年 | 788篇 |
1984年 | 695篇 |
1983年 | 588篇 |
1982年 | 446篇 |
1981年 | 435篇 |
1979年 | 585篇 |
1978年 | 450篇 |
1975年 | 442篇 |
1974年 | 465篇 |
1973年 | 471篇 |
1972年 | 591篇 |
1971年 | 629篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
51.
52.
Eugénie Bassères Giuseppe Coppotelli Thorsten Pfirrmann Jens B. Andersen Maria Masucci Teresa Frisan 《Cellular microbiology》2010,12(11):1622-1633
Invasion of eukaryotic target cells by pathogenic bacteria requires extensive remodelling of the membrane and actin cytoskeleton. Here we show that the remodelling process is regulated by the ubiquitin C‐terminal hydrolase UCH‐L1 that promotes the invasion of epithelial cells by Listeria monocytogenes and Salmonella enterica. Knockdown of UCH‐L1 reduced the uptake of both bacteria, while expression of the catalytically active enzyme promoted efficient internalization in the UCH‐L1‐negative HeLa cell line. The entry of L. monocytogenes involves binding to the receptor tyrosine kinase Met, which leads to receptor phosphorylation and ubiquitination. UCH‐L1 controls the early membrane‐associated events of this triggering cascade since knockdown was associated with altered phosphorylation of the c‐cbl docking site on Tyr1003, reduced ubiquitination of the receptor and altered activation of downstream ERK1/2‐ and AKT‐dependent signalling in response to the natural ligand Hepatocyte Growth Factor (HGF). The regulation of cytoskeleton dynamics was further confirmed by the induction of actin stress fibres in HeLa expressing the active enzyme but not the catalytic mutant UCH‐L1C90S. These findings highlight a previously unrecognized involvement of the ubiquitin cycle in bacterial entry. UCH‐L1 is highly expressed in malignant cells that may therefore be particularly susceptible to invasion by bacteria‐based drug delivery systems. 相似文献
53.
54.
55.
56.
David Skelly 《BMC biology》2010,8(1):136
A new study of divergence in freshwater fish provides strong evidence of rapid, temperature-mediated adaptation. This study
is particularly important in the ongoing debate over the extent and significance of evolutionary response to climate change
because divergence has occurred in relatively few generations in spite of ongoing gene flow and in the aftermath of a significant
genetic bottleneck, factors that have previously been considered obstacles to evolution. Climate change may thus be more likely
to foster contemporary evolutionary responses than has been anticipated, and I argue here for the importance of investigating
their possible occurrence. 相似文献
57.
A Kh Kogan N I Losev A N Kudrin A Mieégombyn 《Biulleten' eksperimental'no? biologii i meditsiny》1984,97(3):270-272
The changes in the size of the myocardial injury area during reperfusion after the coronary occlusion-induced ischemia lasting 30 minutes are phasic in nature. Until 3.5 h the injured area increases and after 23.5 h relatively diminishes. After a more prolonged ischemia such manifestations are either unmarked or absent. Ischemia lasting from 30 min to 4 hours followed by reperfusion, as compared with ischemia of the same duration without reperfusion, normally gives rise to the formation of an area of injury, which is less or occasionally equal in size. The data obtained and reported indicate that in the area of coronary occlusion there are groups of cardiomyocytes that differ as regards the resistance to ischemia. 相似文献
58.
Transcriptional regulatory network triggered by oxidative signals configures the early response mechanisms of japonica rice to chilling stress 总被引:3,自引:0,他引:3
59.
Recent studies have revealed an unexpected synergism between two seemingly unrelated protein families: CCN matricellular proteins
and the tumor necrosis factor (TNF) family of cytokines. CCN proteins are dynamically expressed at sites of injury repair
and inflammation, where TNF cytokines are also expressed. Although TNFα is an apoptotic inducer in some cancer cells, it activates
NFκB to promote survival and proliferation in normal cells, and its cytotoxicity requires inhibition of de novo protein synthesis
or NFκB signaling. The presence of CCN1, CCN2, or CCN3 overrides this requirement and unmasks the apoptotic potential of TNFα,
thus converting TNFα from a proliferation-promoting protein into an apoptotic inducer. These CCN proteins also enhance the
cytotoxicity of other TNF cytokines, including LTα, FasL, and TRAIL. Mechanistically, CCNs function through integrin α6β1 and the heparan sulfate proteoglycan (HSPG) syndecan-4 to induce reactive oxygen species (ROS) accumulation, which is essential
for apoptotic synergism. Mutant CCN1 proteins defective for binding α6β1-HSPGs are unable to induce ROS or apoptotic synergism with TNF cytokines. Further, knockin mice that express an α6β1-HSPG-binding defective CCN1 are blunted in TNFα- and Fas-mediated apoptosis, indicating that CCN1 is a physiologic regulator
of these processes. These findings implicate CCN proteins as contextual regulators of the inflammatory response by dictating
or enhancing the cytotoxicity of TNFα and related cytokines. 相似文献
60.