全文获取类型
收费全文 | 316篇 |
免费 | 26篇 |
国内免费 | 1篇 |
专业分类
343篇 |
出版年
2021年 | 6篇 |
2018年 | 6篇 |
2017年 | 6篇 |
2016年 | 9篇 |
2015年 | 13篇 |
2014年 | 11篇 |
2013年 | 12篇 |
2012年 | 14篇 |
2011年 | 17篇 |
2010年 | 9篇 |
2009年 | 11篇 |
2008年 | 15篇 |
2007年 | 11篇 |
2006年 | 12篇 |
2005年 | 10篇 |
2004年 | 9篇 |
2003年 | 9篇 |
2002年 | 10篇 |
2001年 | 9篇 |
2000年 | 8篇 |
1999年 | 12篇 |
1998年 | 11篇 |
1997年 | 8篇 |
1996年 | 5篇 |
1995年 | 5篇 |
1994年 | 5篇 |
1993年 | 9篇 |
1992年 | 6篇 |
1991年 | 2篇 |
1990年 | 7篇 |
1989年 | 2篇 |
1988年 | 4篇 |
1987年 | 4篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1984年 | 5篇 |
1983年 | 4篇 |
1982年 | 3篇 |
1981年 | 5篇 |
1979年 | 3篇 |
1975年 | 3篇 |
1970年 | 2篇 |
1966年 | 4篇 |
1965年 | 2篇 |
1956年 | 1篇 |
1955年 | 2篇 |
1954年 | 4篇 |
1953年 | 1篇 |
1950年 | 2篇 |
1941年 | 1篇 |
排序方式: 共有343条查询结果,搜索用时 15 毫秒
71.
72.
PAK1 induces podosome formation in A7r5 vascular smooth muscle cells in a PAK-interacting exchange factor-dependent manner 总被引:4,自引:0,他引:4
Webb BA Eves R Crawley SW Zhou S Côté GP Mak AS 《American journal of physiology. Cell physiology》2005,289(4):C898-C907
Remodeling of the vascular smooth muscle cytoskeleton is essential for cell motility involved in the development of diseases such as arteriosclerosis and restenosis. The p21-activated kinase (PAK), which is an effector of the Rho GTPases Rac and Cdc42, has been shown to be involved in cytoskeletal remodeling and cell motility. We show herein that expression of cytoskeletally active constructs of PAK1 is able to induce the formation of dynamic, podosome-like F-actin columns in the A7r5 vascular smooth muscle cell line. Most of these actin columns appear at the junctions between stress fibers and focal adhesions and contain several known podosomal protein markers, such as cortactin, Arp2/3, -actinin, and vinculin. The kinase activity of PAK plays a role in the regulation of the turnover rates of these actin columns but is not essential for their formation. The ability of PAK to interact with the PAK-interacting exchange factor (PIX) but not with Rac or Cdc42, however, is required for the formation of the actin columns as well as for the translocation of PIX and G protein-coupled receptor kinase-interacting protein (GIT) to focal adhesions adjacent to the actin columns. These findings suggest that interaction between PAK and PIX, as well as the recruitment of PIX and GIT to focal adhesions, plays an important role in the formation of actin columns that resemble podosomes induced by phorbol ester in vascular smooth muscle cells. actin cytoskeleton; p21-activated kinase 相似文献
73.
Nathan E. Grega-Larson Scott W. Crawley Amanda L. Erwin Matthew J. Tyska 《Molecular biology of the cell》2015,26(21):3803-3815
Microvilli are actin-based protrusions found on the surface of diverse cell types, where they amplify membrane area and mediate interactions with the external environment. In the intestinal tract, these protrusions play central roles in nutrient absorption and host defense and are therefore essential for maintaining homeostasis. However, the mechanisms controlling microvillar assembly remain poorly understood. Here we report that the multifunctional actin regulator cordon bleu (COBL) promotes the growth of brush border (BB) microvilli. COBL localizes to the base of BB microvilli via a mechanism that requires its proline-rich N-terminus. Knockdown and overexpression studies show that COBL is needed for BB assembly and sufficient to induce microvillar growth using a mechanism that requires functional WH2 domains. We also find that COBL acts downstream of the F-BAR protein syndapin-2, which drives COBL targeting to the apical domain. These results provide insight into a mechanism that regulates microvillar growth during epithelial differentiation and have significant implications for understanding the maintenance of intestinal homeostasis. 相似文献
74.
Hetty C van den Broeck Teun WJM van Herpen Cees Schuit Elma MJ Salentijn Liesbeth Dekking Dirk Bosch Rob J Hamer Marinus JM Smulders Ludovicus JWJ Gilissen Ingrid M van der Meer 《BMC plant biology》2009,9(1):41
Background
Gluten proteins can induce celiac disease (CD) in genetically susceptible individuals. In CD patients gluten-derived peptides are presented to the immune system, which leads to a CD4+ T-cell mediated immune response and inflammation of the small intestine. However, not all gluten proteins contain T-cell stimulatory epitopes. Gluten proteins are encoded by multigene loci present on chromosomes 1 and 6 of the three different genomes of hexaploid bread wheat (Triticum aestivum) (AABBDD). 相似文献75.
The alpha kinases are a widespread family of atypical protein kinases characterized by a novel type of catalytic domain. In this paper the peptide substrate recognition motifs for three alpha kinases, Dictyostelium discoideum myosin heavy chain kinase (MHCK) A and MHCK B and mammalian eukaryotic elongation factor-2 kinase (eEF-2K), were characterized by incorporating amino acid substitutions into a previously identified MHCK A peptide substrate (YAYDTRYRR) (Luo X. et al. (2001) J. Biol. Chem. 276, 17836-43). A lysine or arginine in the P+1 position on the C-terminal side of the phosphoacceptor threonine (P site) was found to be critical for peptide substrate recognition by MHCK A, MHCK B and eEF-2K. Phosphorylation by MHCK B was further enhanced 8-fold by a basic residue in the P+2 position whereas phosphorylation by MHCK A was enhanced 2- to 4-fold by basic residues in the P+2, P+3 and P+4 positions. eEF-2K required basic residues in both the P+1 and P+3 positions to recognize peptide substrates. eEF-2K, like MHCK A and MHCK B, exhibited a strong preference for threonine as the phosphoacceptor amino acid. In contrast, the Dictyostelium VwkA and mammalian TRPM7 alpha kinases phosphorylated both threonine and serine residues. The results, together with a phylogenetic analysis of the alpha kinase catalytic domain, support the view that the metazoan eEF-2Ks and the Dictyostelium MHCKs form a distinct subgroup of alpha kinases with conserved properties. 相似文献
76.
MJ Müller MP Mendon?a IR Oliveira LPL de Oliveira VLS Valente VH Valiati 《Neotropical Entomology》2012,41(2):112-120
We describe for the first time the sexual behavior and the courtship song of males of the African fly Zaprionus indianus (Gupta), a recent invader of South America. The male courtship song is formed by monocyclic pulses and the courtship behavior is simple when compared to that of species of Drosophila. Two interpulse interval (IPI) distributions were observed: pre-mounting and mounting. No significant difference was observed between the pre-mounting IPIs of males that descended from three geographical populations from South America. We also observed the songs produced by females and the homosexual behavior exhibited by males. A sequence of bursts is produced by females as a refusal signal against males, while males emit a characteristic song that identifies sex genus, which differs from the courtship song. The short courtship and mating latencies recorded reveal vigorous males and receptive females, respectively. 相似文献
77.
A phylogenetic analysis of the British flora sheds light on the evolutionary and ecological factors driving plant invasions 下载免费PDF全文
Junying Lim Mick J. Crawley Natasha De Vere Tim Rich Vincent Savolainen 《Ecology and evolution》2014,4(22):4258-4269
Darwin's naturalization hypothesis predicts that invasive species should perform better in their novel range in the absence of close relatives in the native flora due to reduced competition. Evidence from recent taxonomic and phylogenetic‐based studies, however, is equivocal. We test Darwin's naturalization hypothesis at two different spatial scales using a fossil‐dated molecular phylogenetic tree of the British native and alien flora (ca. 1600 species) and extensive, fine‐scale survey data from the 1998 Countryside Survey. At both landscape and local scales, invasive species were neither significantly more nor less related to the native flora than their non‐invasive alien counterparts. Species invasiveness was instead correlated with higher nitrogen and moisture preference, but not other life history traits such as life‐form and height. We argue that invasive species spread in Britain is hence more likely determined by changes in land use and other anthropogenic factors, rather than evolutionary history. Synthesis. The transition from non‐invasive to invasive is not related to phylogenetic distinctiveness to the native community, but instead to their environmental preferences. Therefore, combating biological invasions in the Britain and other industrialized countries need entirely different strategies than in more natural environments. 相似文献
78.
Anna P. Andreou Maria Efthymiou Yao Yu Helena R. Watts Faruq H. Noormohamed Daqing Ma David A. Lane James TB Crawley 《PloS one》2015,10(4)
Ischaemic stroke is caused by occlusive thrombi in the cerebral vasculature. Although tissue-plasminogen activator (tPA) can be administered as thrombolytic therapy, it has major limitations, which include disruption of the blood-brain barrier and an increased risk of bleeding. Treatments that prevent or limit such deleterious effects could be of major clinical importance. Activated protein C (APC) is a natural anticoagulant that regulates thrombin generation, but also confers endothelial cytoprotective effects and improved endothelial barrier function mediated through its cell signalling properties. In murine models of stroke, although APC can limit the deleterious effects of tPA due to its cell signalling function, its anticoagulant actions can further elevate the risk of bleeding. Thus, APC variants such as APC(5A), APC(Ca-ins) and APC(36-39) with reduced anticoagulant, but normal signalling function may have therapeutic benefit. Human and murine protein C (5A), (Ca-ins) and (36-39) variants were expressed and characterised. All protein C variants were secreted normally, but 5-20% of the protein C (Ca-ins) variants were secreted as disulphide-linked dimers. Thrombin generation assays suggested reductions in anticoagulant function of 50- to 57-fold for APC(36-39), 22- to 27-fold for APC(Ca-ins) and 14- to 17-fold for APC(5A). Interestingly, whereas human wt APC, APC(36-39) and APC(Ca-ins) were inhibited similarly by protein C inhibitor (t½ - 33 to 39 mins), APC(5A) was inactivated ~9-fold faster (t½ - 4 mins). Using the murine middle cerebral artery occlusion ischaemia/repurfusion injury model, in combination with tPA, APC(36-39), which cannot be enhanced by its cofactor protein S, significantly improved neurological scores, reduced cerebral infarct area by ~50% and reduced oedema ratio. APC(36-39) also significantly reduced bleeding in the brain induced by administration of tPA, whereas wt APC did not. If our data can be extrapolated to clinical settings, then APC(36-39) could represent a feasible adjunctive therapy for ischaemic stroke. 相似文献
79.
80.
Kai Yu Zhang Angela E Kedgley Claire R Donoghue Daniel Rueckert Anthony MJ Bull 《Arthritis research & therapy》2014,16(1):R27