全文获取类型
收费全文 | 4830篇 |
免费 | 478篇 |
国内免费 | 2篇 |
专业分类
5310篇 |
出版年
2023年 | 18篇 |
2022年 | 59篇 |
2021年 | 122篇 |
2020年 | 63篇 |
2019年 | 77篇 |
2018年 | 94篇 |
2017年 | 91篇 |
2016年 | 166篇 |
2015年 | 219篇 |
2014年 | 273篇 |
2013年 | 300篇 |
2012年 | 386篇 |
2011年 | 363篇 |
2010年 | 241篇 |
2009年 | 197篇 |
2008年 | 292篇 |
2007年 | 285篇 |
2006年 | 246篇 |
2005年 | 244篇 |
2004年 | 193篇 |
2003年 | 177篇 |
2002年 | 169篇 |
2001年 | 56篇 |
2000年 | 41篇 |
1999年 | 45篇 |
1998年 | 39篇 |
1997年 | 31篇 |
1996年 | 36篇 |
1994年 | 23篇 |
1993年 | 28篇 |
1992年 | 33篇 |
1991年 | 36篇 |
1990年 | 29篇 |
1989年 | 33篇 |
1988年 | 33篇 |
1987年 | 25篇 |
1986年 | 32篇 |
1985年 | 38篇 |
1984年 | 29篇 |
1983年 | 32篇 |
1982年 | 29篇 |
1981年 | 29篇 |
1980年 | 21篇 |
1979年 | 21篇 |
1978年 | 25篇 |
1977年 | 20篇 |
1976年 | 23篇 |
1974年 | 28篇 |
1973年 | 20篇 |
1972年 | 17篇 |
排序方式: 共有5310条查询结果,搜索用时 15 毫秒
921.
922.
923.
Marc-Thorsten Hütt Marcus Kaiser Claus C. Hilgetag 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2014,369(1653)
The understanding of neural activity patterns is fundamentally linked to an understanding of how the brain''s network architecture shapes dynamical processes. Established approaches rely mostly on deviations of a given network from certain classes of random graphs. Hypotheses about the supposed role of prominent topological features (for instance, the roles of modularity, network motifs or hierarchical network organization) are derived from these deviations. An alternative strategy could be to study deviations of network architectures from regular graphs (rings and lattices) and consider the implications of such deviations for self-organized dynamic patterns on the network. Following this strategy, we draw on the theory of spatio-temporal pattern formation and propose a novel perspective for analysing dynamics on networks, by evaluating how the self-organized dynamics are confined by network architecture to a small set of permissible collective states. In particular, we discuss the role of prominent topological features of brain connectivity, such as hubs, modules and hierarchy, in shaping activity patterns. We illustrate the notion of network-guided pattern formation with numerical simulations and outline how it can facilitate the understanding of neural dynamics. 相似文献
924.
925.
926.
Marcus E Peter 《Cell cycle (Georgetown, Tex.)》2014,13(9):1373-1378
The conventional view of CD95 (Fas/APO-1) is that it is a dedicated apoptosis-inducing receptor with important functions in immune cell homeostasis and in viral and tumor defense. There is an emerging recognition, however, that CD95 also has multiple non-apoptotic activities. In the context of cancer, CD95 was shown to have tumor-promoting activities, and the concept of this new function of CD95 in cancer is gaining traction. Recently, we showed that not only is CD95 a growth promoter for cancer cells, but, paradoxically, when either CD95 or CD95 ligand (CD95L) is removed, that virtually all cancer cells die through a process we have named DICE (death induced by CD95R/L elimination). In this perspective, I outline a hypothesis regarding the physiological function of DICE, and why it may be possible to use induction of DICE to treat many, if not most, cancers. 相似文献
927.
Bruno Otero Marcus Degerman Thomas Budde Hansen Ernst Broberg Hansen Bernt Nilsson 《Bioprocess and biosystems engineering》2014,37(10):1989-1996
This paper presents the design of a two-step process in which the first step is PEGylation of a protein, and the second step is chromatographic purification of the target mono-PEGylated protein from the unreacted and the di-PEGylated impurities. The difference between optimizing each process step separately and optimizing them simultaneously is studied. It was found that by optimizing the steps simultaneously up to a 100 % increase in productivity could be obtained without reduction in yield. Optimizing both steps at the same time makes it possible for the optimization method to take into account that the di-PEGylated protein is much easier to separate than the non-PEGylated protein. The easier separation makes it possible to get a higher yield and productivity at the same time. The effect of recycling was also studied and the yield could be increased by 30 % by recycling the unreacted protein. However, if maximum productivity is required, batch mode is preferable. 相似文献
928.
929.
Yinghui Zhou William M. Rideout III Angela Bressel Sireesha Yalavarthi Tong Zi Darren Potz Samuel Farlow Joelle Brodeur Anthony Monti Shailaja Reddipalli Qiurong Xiao Steve Bottega Bin Feng M. Isabel Chiu Marcus Bosenberg Joerg Heyer 《PloS one》2014,9(8)
Colon cancer is the second most common cause of cancer mortality in the Western world with metastasis commonly present at the time of diagnosis. Screening for propagation and metastatic behavior in a novel chimeric-mouse colon cancer model, driven by mutant p53 and β-Catenin, led to the identification of a unique, invasive adenocarcinoma. Comparison of the genome of this tumor, CB42, with genomes from non-propagating tumors by array CGH and sequencing revealed an amplicon on chromosome five containing CDK6 and CDK14, and a KRAS mutation, respectively. Single agent small molecule inhibition of either CDK6 or MEK, a kinase downstream of KRAS, led to tumor growth inhibition in vivo whereas combination therapy not only led to regression of the subcutaneous tumors, but also near complete inhibition of lung metastasis; thus, genomic analysis of this tumor led to effective, individualized treatment. 相似文献
930.
Histamine (HA) is recognized by its target cells via four G-protein-coupled receptors, referred to as histamine H1-receptor (H1R), H2R, H3R, and H4R. Both H1R and H4R exert pro-inflammatory functions. However, their signal transduction pathways have never been analyzed in a directly comparable manner side by side. Moreover, the analysis of pharmacological properties of the murine orthologs, representing the main targets of pre-clinical research, is very important. Therefore, we engineered recombinant HEK293 cells expressing either mouse (m)H1R or mH4R at similar levels and analyzed HA-induced signalling in these cells. HA induced intracellular calcium mobilization via both mH1R and mH4R, with the mH1R being much more effective. Whereas cAMP accumulation was potentiated via the mH1R, it was reduced via the mH4R. The regulation of both second messengers via the H4R, but not the H1R, was sensitive to pertussis toxin (PTX). The mitogen-activated protein kinases (MAPKs) ERK 1/2 were massively activated downstream of both receptors and demonstrated a functional involvement in HA-induced EGR-1 gene expression. The p38 MAPK was moderately activated via both receptors as well, but was functionally involved in HA-induced EGR-1 gene expression only in H4R-expressing cells. Surprisingly, in this system p38 MAPK activity reduced the HA-induced gene expression. In summary, using this system which allows a direct comparison of mH1R- and mH4R-induced signalling, qualitative and quantitative differences on the levels of second messenger generation and also in terms of p38 MAPK function became evident. 相似文献