全文获取类型
收费全文 | 10588篇 |
免费 | 840篇 |
国内免费 | 2篇 |
出版年
2023年 | 62篇 |
2022年 | 42篇 |
2021年 | 224篇 |
2020年 | 172篇 |
2019年 | 169篇 |
2018年 | 231篇 |
2017年 | 207篇 |
2016年 | 324篇 |
2015年 | 554篇 |
2014年 | 599篇 |
2013年 | 701篇 |
2012年 | 927篇 |
2011年 | 841篇 |
2010年 | 528篇 |
2009年 | 441篇 |
2008年 | 668篇 |
2007年 | 567篇 |
2006年 | 552篇 |
2005年 | 477篇 |
2004年 | 452篇 |
2003年 | 371篇 |
2002年 | 391篇 |
2001年 | 168篇 |
2000年 | 147篇 |
1999年 | 123篇 |
1998年 | 64篇 |
1997年 | 51篇 |
1996年 | 61篇 |
1995年 | 56篇 |
1994年 | 41篇 |
1993年 | 32篇 |
1992年 | 96篇 |
1991年 | 97篇 |
1990年 | 66篇 |
1989年 | 62篇 |
1988年 | 49篇 |
1987年 | 50篇 |
1986年 | 68篇 |
1985年 | 42篇 |
1984年 | 35篇 |
1983年 | 27篇 |
1981年 | 36篇 |
1980年 | 25篇 |
1979年 | 32篇 |
1978年 | 31篇 |
1977年 | 36篇 |
1976年 | 27篇 |
1975年 | 35篇 |
1973年 | 36篇 |
1971年 | 33篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
1.
2.
Athanassios Alevizopoulos Nicolas Mermod 《BioEssays : news and reviews in molecular, cellular and developmental biology》1997,19(7):581-591
Transforming growth factor-β (TGF-β) and its related proteins regulate broad aspects of body development, including cell proliferation, differentiation, apoptosis and gene expression, in various organisms. Deregulated TGF-β function has been causally implicated in the generation of human fibrotic disorders and in tumor progression. Nevertheless, the molecular mechanisms of TGF-β action remained essentially unknown until recently. Here, we discuss recent progress in our understanding of the mechanism of TGF-β signal transduction with respect to the regulation of gene expression, the control of cell phenotype and the potential usage TGF-β for the treatment of human diseases. 相似文献
3.
4.
Clémence L. Gamblin émilie J.-L. Hardy Fran?ois J.-M. Chartier Nicolas Bisson Patrick Laprise 《The Journal of cell biology》2014,204(4):487-495
During epithelial cell polarization, Yurt (Yrt) is initially confined to the lateral membrane and supports the stability of this membrane domain by repressing the Crumbs-containing apical machinery. At late stages of embryogenesis, the apical recruitment of Yrt restricts the size of the apical membrane. However, the molecular basis sustaining the spatiotemporal dynamics of Yrt remains undefined. In this paper, we report that atypical protein kinase C (aPKC) phosphorylates Yrt to prevent its premature apical localization. A nonphosphorylatable version of Yrt dominantly dismantles the apical domain, showing that its aPKC-mediated exclusion is crucial for epithelial cell polarity. In return, Yrt counteracts aPKC functions to prevent apicalization of the plasma membrane. The ability of Yrt to bind and restrain aPKC signaling is central for its role in polarity, as removal of the aPKC binding site neutralizes Yrt activity. Thus, Yrt and aPKC are involved in a reciprocal antagonistic regulatory loop that contributes to segregation of distinct and mutually exclusive membrane domains in epithelial cells. 相似文献
5.
Liakos Panagiotis; Bourmeyster Nicolas; Defaye Genevieve; Chambaz Edmond M.; Bottari Serge P. 《American journal of physiology. Cell physiology》1997,273(4):C1324
Angiotensin II(ANG II) has long been known for its pressor and growth-promotingeffects, which are both mediated by theAT1 receptor. By contrast, theAT2 receptor has recently beenreported to mediate inhibition of proliferation through as yetundefined mechanisms. We report here that in bovine adrenal fasciculata cells ANG II by itself does not affect growth but inhibits basic fibroblast growth factor (bFGF)-induced DNA synthesis and blocks thecells in G1 phase. Consistent withthis, ANG II inhibits cyclin D1 expression and cyclinD1-associated kinase activity. Theantimitogenic effect of ANG II is partly mimicked by theAT2-selective agonist CGP-42112.It is also blocked partly and in an additive fashion by theAT1- andAT2-selective antagonists losartanand PD-123319, indicating the contribution of both receptor subtypes tothis response. AT1-dependentantiproliferation is selectively blocked by the cyclooxygenaseinhibitor indomethacin and restored by prostaglandin E2, whereasAT2-receptor-mediated inhibitionof growth is suppressed by the tyrosine phosphatase inhibitorsorthovanadate and bpV(pic). Both pathways are, however,pertussis toxin sensitive. We hypothesize that, in fasciculatacells, the AT1 receptor inhibitsbFGF-induced proliferation by stimulating prostaglandin synthesis,whereas the AT2 receptor mediatesits effect through a pathway that requires protein tyrosine phosphataseactivation. 相似文献
6.
7.
8.
Ralf Heinrich Peter Bräunig Ismeni Walter Henning Schneider Edward A. Kravitz 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2000,186(7-8):617-629
In the American lobster (Homarus americanus) the biogenic amines serotonin and octopamine appear to play important and opposite roles in the regulation of aggressive behavior, in the establishment and/or maintenance of dominant and subordinate behavioral states and in the modulation of the associated postural stances and escape responses. The octopamine-containing neurosecretory neurons in the thoracic regions of the lobster ventral nerve cord fall into two morphological subgroups, the root octopamine cells, a classical neurohemal group with release regions along second thoracic roots, and the claw octopamine cells, a group that selectively innervates the claws. Cells of both subgroups have additional sets of endings within neuropil regions of ganglia of the ventral nerve cord. Octopamine neurosecretory neurons generally are silent, but when spontaneously active or when activated, they show large overshooting action potentials with prominent after-hyperpolarizations. Autoinhibition after high-frequency firing, which is also seen in other crustacean neurosecretory cells, is readily apparent in these cells. The cells show no spontaneous synaptic activity, but appear to be excited by a unitary source. Stimulation of lateral or medial giant axons, which excite serotonergic cells yielded no response in octopaminergic neurosecretory cells and no evidence for direct interactions between pairs of octopamine neurons, or between the octopaminergic and the serotonergic sets of neurosecretory neurons was found. 相似文献
9.
Nathan D. Mathewson Orr Ashenberg Itay Tirosh Simon Gritsch Elizabeth M. Perez Sascha Marx Livnat Jerby-Arnon Rony Chanoch-Myers Toshiro Hara Alyssa R. Richman Yoshinaga Ito Jason Pyrdol Mirco Friedrich Kathrin Schumann Michael J. Poitras Prafulla C. Gokhale L. Nicolas Gonzalez Castro Marni E. Shore Kai W. Wucherpfennig 《Cell》2021,184(5):1281-1298.e26
10.
Arhamatoulaye Ma?ga Jon Merlin Elodie Marcon Céline Rouget Maud Larregola Bernard Gilquin Carole Fruchart-Gaillard Evelyne Lajeunesse Charles Marchetti Alain Lorphelin Laurent Bellanger Roger J. Summers Dana S. Hutchinson Bronwyn A. Evans Denis Servent Nicolas Gilles 《PloS one》2013,8(7)
ρ-Da1a is a three-finger fold toxin from green mamba venom that is highly selective for the α1A-adrenoceptor. This toxin has atypical pharmacological properties, including incomplete inhibition of 3H-prazosin or 125I-HEAT binding and insurmountable antagonist action. We aimed to clarify its mode of action at the α1A-adrenoceptor. The affinity (pKi 9.26) and selectivity of ρ-Da1a for the α1A-adrenoceptor were confirmed by comparing binding to human adrenoceptors expressed in eukaryotic cells. Equilibrium and kinetic binding experiments were used to demonstrate that ρ-Da1a, prazosin and HEAT compete at the α1A-adrenoceptor. ρ-Da1a did not affect the dissociation kinetics of 3H-prazosin or 125I-HEAT, and the IC50 of ρ-Da1a, determined by competition experiments, increased linearly with the concentration of radioligands used, while the residual binding by ρ-Da1a remained stable. The effect of ρ-Da1a on agonist-stimulated Ca2+ release was insurmountable in the presence of phenethylamine- or imidazoline-type agonists. Ten mutations in the orthosteric binding pocket of the α1A-adrenoceptor were evaluated for alterations in ρ-Da1a affinity. The D1063.32A and the S1885.42A/S1925.46A receptor mutations reduced toxin affinity moderately (6 and 7.6 times, respectively), while the F862.64A, F2886.51A and F3127.39A mutations diminished it dramatically by 18- to 93-fold. In addition, residue F862.64 was identified as a key interaction point for 125I-HEAT, as the variant F862.64A induced a 23-fold reduction in HEAT affinity. Unlike the M1 muscarinic acetylcholine receptor toxin MT7, ρ-Da1a interacts with the human α1A-adrenoceptor orthosteric pocket and shares receptor interaction points with antagonist (F862.64, F2886.51 and F3127.39) and agonist (F2886.51 and F3127.39) ligands. Its selectivity for the α1A-adrenoceptor may result, at least partly, from its interaction with the residue F862.64, which appears to be important also for HEAT binding. 相似文献