全文获取类型
收费全文 | 2449篇 |
免费 | 211篇 |
专业分类
2660篇 |
出版年
2023年 | 4篇 |
2022年 | 18篇 |
2021年 | 49篇 |
2020年 | 17篇 |
2019年 | 20篇 |
2018年 | 32篇 |
2017年 | 35篇 |
2016年 | 76篇 |
2015年 | 116篇 |
2014年 | 130篇 |
2013年 | 144篇 |
2012年 | 218篇 |
2011年 | 205篇 |
2010年 | 151篇 |
2009年 | 131篇 |
2008年 | 141篇 |
2007年 | 156篇 |
2006年 | 136篇 |
2005年 | 123篇 |
2004年 | 147篇 |
2003年 | 124篇 |
2002年 | 128篇 |
2001年 | 30篇 |
2000年 | 20篇 |
1999年 | 31篇 |
1998年 | 39篇 |
1997年 | 23篇 |
1996年 | 19篇 |
1995年 | 20篇 |
1994年 | 20篇 |
1993年 | 22篇 |
1992年 | 18篇 |
1991年 | 12篇 |
1990年 | 11篇 |
1989年 | 16篇 |
1988年 | 7篇 |
1987年 | 7篇 |
1986年 | 9篇 |
1985年 | 4篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1982年 | 7篇 |
1981年 | 5篇 |
1980年 | 4篇 |
1979年 | 5篇 |
1978年 | 5篇 |
1977年 | 4篇 |
1975年 | 3篇 |
1974年 | 3篇 |
1973年 | 3篇 |
排序方式: 共有2660条查询结果,搜索用时 13 毫秒
41.
Mokkapati S Fleger-Weckmann A Bechtel M Koch M Breitkreutz D Mayer U Smyth N Nischt R 《The Journal of biological chemistry》2011,286(3):1911-1918
The nidogen-laminin interaction is proposed to play a key role in basement membrane (BM) assembly. However, though there are similarities, the phenotypes in mice lacking nidogen 1 and 2 (nidogen double null) differ to those of mice lacking the nidogen binding module (γ1III4) of the laminin γ1 chain. This indicates different cell- and tissue-specific functions for nidogens and their interaction with laminin and poses the question of whether the phenotypes in nidogen double null mice are caused by the loss of the laminin-nidogen interaction or rather by other unknown nidogen functions. To investigate this, we analyzed BMs, in particular those in the skin of mice lacking the nidogen binding module. In contrast to nidogen double null mice, all skin BMs in γ1III4-deficient mice appeared normal. Furthermore, although nidogen 1 deposition was strongly reduced, nidogen 2 appeared unchanged. Mice with additional deletion of the laminin γ3 chain, which contains a γ1-like nidogen binding module, showed a further reduction of nidogen 1 in the dermoepidermal BM; however, this again did not affect nidogen 2. This demonstrates that in vivo only nidogen 1 deposition is critically dependent on the nidogen binding modules of the laminin γ1 and γ3 chains, whereas nidogen 2 is independently recruited either by binding to an alternative site on laminin or to other BM proteins. 相似文献
42.
Many protein kinases are activated by a conserved regulatory step involving T-loop phosphorylation. Although there is considerable focus on kinase activator proteins, the importance of specific T-loop phosphatases reversing kinase activation has been underappreciated. We find that the protein phosphatase 6 (PP6) holoenzyme is the major T-loop phosphatase for Aurora A, an essential mitotic kinase. Loss of PP6 function by depletion of catalytic or regulatory subunits interferes with spindle formation and chromosome alignment because of increased Aurora A activity. Aurora A T-loop phosphorylation and the stability of the Aurora A-TPX2 complex are increased in cells depleted of PP6 but not other phosphatases. Furthermore, purified PP6 acts as a T-loop phosphatase for Aurora A-TPX2 complexes in vitro, whereas catalytically inactive mutants cannot dephosphorylate Aurora A or rescue the PPP6C depletion phenotype. These results demonstrate a hitherto unappreciated role for PP6 as the T-loop phosphatase regulating Aurora A activity during spindle formation and suggest the general importance of this form of regulation. 相似文献
43.
Ulrike Herzschuh H. John B. Birks Xingqi Liu Claudia Kubatzki Gerrit Lohmann 《Global Ecology and Biogeography》2010,19(2):278-286
Aim Atmospheric CO2 concentrations depend, in part, on the amount of biomass locked up in terrestrial vegetation. Information on the causes of a broad‐scale vegetation transition and associated loss of biomass is thus of critical interest for understanding global palaeoclimatic changes. Pollen records from the north‐eastern Tibet‐Qinghai Plateau reveal a dramatic and extensive forest decline beginning c. 6000 cal. yr bp . The aim of this study is to elucidate the causes of this regional‐scale change from high‐biomass forest to low‐biomass steppe on the Tibet‐Qinghai Plateau during the second half of the Holocene. Location Our study focuses on the north‐eastern Tibet‐Qinghai Plateau. Stratigraphical data used are from Qinghai Lake (3200 m a.s.l., 36°32′–37°15′ N, 99°36′–100°47′ E). Methods We apply a modern pollen‐precipitation transfer function from the eastern and north‐eastern Tibet‐Qinghai Plateau to fossil pollen spectra from Qinghai Lake to reconstruct annual precipitation changes during the Holocene. The reconstructions are compared to a stable oxygen‐isotope record from the same sediment core and to results from two transient climate model simulations. Results The pollen‐based precipitation reconstruction covering the Holocene parallels moisture changes inferred from the stable oxygen‐isotope record. Furthermore, these results are in close agreement with simulated model‐based past annual precipitation changes. Main conclusions In the light of these data and the model results, we conclude that it is not necessary to attribute the broad‐scale forest decline to human activity. Climate change as a result of changes in the intensity of the East Asian Summer Monsoon in the mid‐Holocene is the most parsimonious explanation for the widespread forest decline on the Tibet‐Qinghai Plateau. Moreover, climate feedback from a reduced forest cover accentuates increasingly drier conditions in the area, indicating complex vegetation–climate interactions during this major ecological change. 相似文献
44.
Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation 总被引:19,自引:0,他引:19
Fiedler U Reiss Y Scharpfenecker M Grunow V Koidl S Thurston G Gale NW Witzenrath M Rosseau S Suttorp N Sobke A Herrmann M Preissner KT Vajkoczy P Augustin HG 《Nature medicine》2006,12(2):235-239
The angiopoietins Ang-1 and Ang-2 have been identified as ligands of the receptor tyrosine kinase Tie-2 (refs. 1,2). Paracrine Ang-1-mediated activation of Tie-2 acts as a regulator of vessel maturation and vascular quiescence. In turn, the antagonistic ligand Ang-2 acts by an autocrine mechanism and is stored in endothelial Weibel-Palade bodies from where it can be rapidly released upon stimulation. The rapid release of Ang-2 implies functions of the angiopoietin-Tie system beyond its established role during vascular morphogenesis as a regulator of rapid vascular responses. Here we show that mice deficient in Ang-2 (encoded by the gene Angpt2) cannot elicit an inflammatory response in thioglycollate-induced or Staphylococcus aureus-induced peritonitis, or in the dorsal skinfold chamber model. Recombinant Ang-2 restores the inflammation defect in Angpt2(-/-) mice. Intravital microscopy showed normal TNF-alpha-induced leukocyte rolling in the vasculature of Angpt2(-/-)mice, but rolling cells did not firmly adhere to activated endothelium. Cellular experiments showed that Ang-2 promotes adhesion by sensitizing endothelial cells toward TNF-alpha and modulating TNF-alpha-induced expression of endothelial cell adhesion molecules. Together, these findings identify Ang-2 as an autocrine regulator of endothelial cell inflammatory responses. Ang-2 thereby acts as a switch of vascular responsiveness exerting a permissive role for the activities of proinflammatory cytokines. 相似文献
45.
Brockstedt U Uzarowska A Montpetit A Pfau W Labuda D 《Biochemical and biophysical research communications》2004,313(4):1004-1008
The modification of cellular DNA by environmental substances is thought to be a crucial event in chemical induced carcinogenesis. Among the environmental carcinogens, aromatic amines are known for the fact that they can induce several types of cancers through the formation of so-called DNA adducts. We took advantage of the potential of the SELEX method to select for highly specific RNA ligands that recognize specific genotoxic aromatic amines. The aromatic amine 4,4'-methylenedianiline (MDA) was used as a target. Following in vitro selection, we obtained specific MDA-binding RNA molecules based on an affinity chromatography assay. These results open the possibility of using the SELEX technique to generate RNA molecules as diagnostic tools for the detection of DNA damaging compounds and ultimately DNA adducts. 相似文献
46.
47.
Anja K. Dunsch Dean Hammond Jennifer Lloyd Lothar Schermelleh Ulrike Gruneberg Francis A. Barr 《The Journal of cell biology》2012,198(6):1039-1054
The cytoplasmic dynein motor generates pulling forces to center and orient the mitotic spindle within the cell. During this positioning process, dynein oscillates from one pole of the cell cortex to the other but only accumulates at the pole farthest from the spindle. Here, we show that dynein light chain 1 (DYNLL1) is required for this asymmetric cortical localization of dynein and has a specific function defining spindle orientation. DYNLL1 interacted with a spindle-microtubule–associated adaptor formed by CHICA and HMMR via TQT motifs in CHICA. In cells depleted of CHICA or HMMR, the mitotic spindle failed to orient correctly in relation to the growth surface. Furthermore, CHICA TQT motif mutants localized to the mitotic spindle but failed to recruit DYNLL1 to spindle microtubules and did not correct the spindle orientation or dynein localization defects. These findings support a model where DYNLL1 and CHICA-HMMR form part of the regulatory system feeding back spindle position to dynein at the cell cortex. 相似文献
48.
49.
Summary Lymphocyte karyotyping of an infant girl with the clinical features of microphthalmia, iridoschisis, goiter, hip joint dysplasia, labium synechia and craniotabes revealed an Xp deletion. The lymphocyte karyotypes of the parents were normal. Bromodeoxyuridine incorporation studies showed that, in 42 out of 43 metaphases, the deleted X chromosome was late replicating. In one metaphase, the normal X chromosome was observed to be allocyclic. Using DNA markers from the Xp22 region, the breakpoint was assigned distal to DXS16 (pXUT23) and proximal to DXS143 (dic56). Dosage intensity measurements confirmed that the STS gene and the DNA marker DXS31 were involved in the deleted area. Restriction fragment length polymorphism analysis revealed that the paternally derived X-chromosome was deleted. 相似文献
50.
U Mütze S Beblo L Kortz C Matthies B Koletzko M Bruegel C Rohde J Thiery W Kiess U Ceglarek 《PloS one》2012,7(8):e43021