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排序方式: 共有168条查询结果,搜索用时 377 毫秒
41.
Christophe Le Clainche Satya Prakash Dwivedi Dominique Didry Marie-France Carlier 《The Journal of biological chemistry》2010,285(30):23420-23432
The focal adhesion protein vinculin is an actin-binding protein involved in the mechanical coupling between the actin cytoskeleton and the extracellular matrix. An autoinhibitory interaction between the N-terminal head (Vh) and the C-terminal tail (Vt) of vinculin masks an actin filament side-binding domain in Vt. The binding of several proteins to Vh disrupts this intramolecular interaction and exposes the actin filament side-binding domain. Here, by combining kinetic assays and microscopy observations, we show that Vt inhibits actin polymerization by blocking the barbed ends of actin filaments. In low salt conditions, Vt nucleates actin filaments capped at their barbed ends. We determined that the interaction between vinculin and the barbed end is characterized by slow association and dissociation rate constants. This barbed end capping activity requires C-terminal amino acids of Vt that are dispensable for actin filament side binding. Like the side-binding domain, the capping domain of vinculin is masked by an autoinhibitory interaction between Vh and Vt. In contrast to the side-binding domain, the capping domain is not unmasked by the binding of a talin domain to Vh and requires the dissociation of an additional autoinhibitory interaction. Finally, we show that vinculin and the formin mDia1, which is involved in the processive elongation of actin filaments in focal adhesions, compete for actin filament barbed ends. 相似文献
42.
Maud Hertzog Francesca Milanesi Larnele Hazelwood Andrea Disanza HongJun Liu Emilie Perlade Maria Grazia Malabarba Sebastiano Pasqualato Alessio Maiolica Stefano Confalonieri Christophe Le Clainche Nina Offenhauser Jennifer Block Klemens Rottner Pier Paolo Di Fiore Marie-France Carlier Niels Volkmann Dorit Hanein Giorgio Scita 《PLoS biology》2010,8(6)
Actin capping and cross-linking proteins regulate the dynamics and architectures
of different cellular protrusions. Eps8 is the founding member of a unique
family of capping proteins capable of side-binding and bundling actin filaments.
However, the structural basis through which Eps8 exerts these functions remains
elusive. Here, we combined biochemical, molecular, and genetic approaches with
electron microscopy and image analysis to dissect the molecular mechanism
responsible for the distinct activities of Eps8. We propose that bundling
activity of Eps8 is mainly mediated by a compact four helix bundle, which is
contacting three actin subunits along the filament. The capping activity is
mainly mediated by a amphipathic helix that binds within the hydrophobic pocket
at the barbed ends of actin blocking further addition of actin monomers.
Single-point mutagenesis validated these modes of binding, permitting us to
dissect Eps8 capping from bundling activity in vitro. We further showed that the
capping and bundling activities of Eps8 can be fully dissected in vivo,
demonstrating the physiological relevance of the identified Eps8
structural/functional modules. Eps8 controls actin-based motility through its
capping activity, while, as a bundler, is essential for proper intestinal
morphogenesis of developing Caenorhabditis elegans. 相似文献
43.
M. BÉRUBÉ A. AGUILAR D. DENDANTO F. LARSEN G. NOTARBARTOLO DI SCIARA R. SEARS J. SIGURJÓNSSON J. URBAN-R & P. J. PALSBØLL 《Molecular ecology》1998,7(5):585-599
Samples were collected from 407 fin whales, Balaenoptera physalus , at four North Atlantic and one Mediterranean Sea summer feeding area as well as the Sea of Cortez in the Pacific Ocean. For each sample, the sex, the sequence of the first 288 nucleotides of the mitochondrial (mt) control region and the genotype at six microsatellite loci were determined. A significant degree of divergence was detected at all nuclear and mt loci between North Atlantic/Mediterranean Sea and the Sea of Cortez. However, the divergence time estimated from the mt sequences was substantially lower than the time elapsed since the rise of the Panama Isthmus, suggesting occasional gene flow between the North Pacific and North Atlantic ocean after the separation of the two oceans. Within the North Atlantic and Mediterranean Sea, significant levels of heterogeneity were observed in the mtDNA between the Mediterranean Sea, the eastern (Spain) and the western (the Gulf of Maine and the Gulf of St Lawrence) North Atlantic. Samples collected off West Greenland and Iceland could not be unequivocally assigned to either of the two areas. The homogeneity tests performed using the nuclear data revealed significant levels of divergence only between the Mediterranean Sea and the Gulf of St Lawrence or West Greenland. In conclusion, our results suggest the existence of several recently diverged populations in the North Atlantic and Mediterranean Sea, possibly with some limited gene flow between adjacent populations, a population structure which is consistent with earlier population models proposed by Kellogg, Ingebrigtsen, and Sergeant. 相似文献
44.
O. Plantard J.-Y. Rasplus G. Mondor I. Le Clainche M. Solignac 《Proceedings. Biological sciences / The Royal Society》1998,265(1401):1075
Cynipids are known to use various reproductive modes (arrhenotoky, thelytoky and strict cyclical parthenogenesis), but the mechanism remains unknown. We have studied the reproductive system of a rose gallwasp, Diplolepis spinosissimae, which was found to exhibit two different reproductive systems according to the population. In eight out of the ten populations studied, all along the Atlantic coast, D. spinosissimae is thelytokous. Males are extremely rare, and all females are homozygous at three microsatellite loci. ''Obligate homozygous parthenogenesis'' was found to be strictly associated with the presence of the endosymbiotic bacterium Wolbachia sp. In the two remaining populations, deprived of Wolbachia, D. spinosissimae reproduced by arrhenotoky as indicated by the larger frequency of males and heterozygosity of females. Allelic diversity, although not zero, was highly reduced in the coastal populations, as a consequence of thelytoky and gamete duplication. We hypothesize that mating of uninfected males with infected females during the first generations after an infection event could explain the small but significant amount of polymorphism observed in those populations. The high level of differentiation indicates a low gene flow, even between geographically close coastal populations. 相似文献
45.
C. ÖFNER A. HITTMAIR I. KRÖLL I. BANGERL W. ZECHMANN M. TÖTSCH D. LADURNER† W. BÖCKER‡ K. W. SCHMID‡ 《Cytopathology》1994,5(1):33-40
Between 1977 and 1989 252 fine needle aspirates (FNAs) of the thyroid from patients with a clinical suspicion of subacute granulomatous (de Quervain's) thyroiditis were examined in the Department of Pathology of the University of Innsbruck, Austria. In the same period 31 cases with preoperative FNA were diagnosed histologically as subacute thyroiditis. Only in three of these cases were the cytological features of de Quervain's thyroiditis found in the preoperative FNA. However, in 13 of these 31 cases a cytological suspicion of malignancy was obtained. Subsequent histological examination revealed an acute phase inflammation of de Quervain's thyroiditis in most of these cases. We conclude that an accurate FNA diagnosis of de Quervain's thyroiditis, particularly in the acute stage, may cause difficulties due to a lack of typical features and the appearance of atypical thyroid follicular cells. For the cytopathologist, accurate clinical information relating to the possibility of de Quervain's thyroiditis is essential if unnecessary surgery is to be avoided. 相似文献
46.
47.
48.
GRB2 links signaling to actin assembly by enhancing interaction of neural Wiskott-Aldrich syndrome protein (N-WASp) with actin-related protein (ARP2/3) complex 总被引:11,自引:0,他引:11
Carlier MF Nioche P Broutin-L'Hermite I Boujemaa R Le Clainche C Egile C Garbay C Ducruix A Sansonetti P Pantaloni D 《The Journal of biological chemistry》2000,275(29):21946-21952
Proteins of the Wiskott-Aldrich Syndrome protein (WASp) family connect signaling pathways to the actin polymerization-driven cell motility. The ubiquitous homolog of WASp, N-WASp, is a multidomain protein that interacts with the Arp2/3 complex and G-actin via its C-terminal WA domain to stimulate actin polymerization. The activity of N-WASp is enhanced by the binding of effectors like Cdc42-guanosine 5'-3-O-(thio)triphosphate, phosphatidylinositol bisphosphate, or the Shigella IcsA protein. Here we show that the SH3-SH2-SH3 adaptor Grb2 is another activator of N-WASp that stimulates actin polymerization by increasing the amount of N-WASp. Arp2/3 complex. The concentration dependence of N-WASp activity, sedimentation velocity and cross-linking experiments together suggest that N-WASp is subject to self-association, and Grb2 enhances N-WASp activity by binding preferentially to its active monomeric form. Use of peptide inhibitors, mutated Grb2, and isolated SH3 domains demonstrate that the effect of Grb2 is mediated by the interaction of its C-terminal SH3 domain with the proline-rich region of N-WASp. Cdc42 and Grb2 bind simultaneously to N-WASp and enhance actin polymerization synergistically. Grb2 shortens the delay preceding the onset of Escherichia coli (IcsA) actin-based reconstituted movement. These results suggest that Grb2 may activate Arp2/3 complex-mediated actin polymerization downstream from the receptor tyrosine kinase signaling pathway. 相似文献
49.
Proteins of the Wiskott-Aldrich syndrome and Ena/VASP families both play essential functions in the regulation of actin dynamics at the cell leading edge. However, possibilities of functional interplay between members of these two families have not been addressed. Here we show that, in hemopoietic cells, recruitment of the C-terminal VCA (Verprolin homology, Cofilin homology, Acidic) domain of WASp at the plasma membrane by a ligand technique using rapamycin as an intermediate is not sufficient to elicit efficient Arp2/3 complex-mediated actin polymerization. Other domains of WASp, in particular the proline-rich domain, are required for the formation of actin-rich structures. An in vitro analysis demonstrates that the proline-rich domain of WASp binds VASP with an affinity of approximately 10(6) M(-1). In addition, WASp and VASP both accumulate in actin-rich phagocytic cups. Finally, in a reconstituted motility medium, VASP enhances actin-based propulsion of WASp-coated beads in a fashion reminiscent of its effect on Listeria movement. We propose that VASP and WASp cooperation is essential in stimulating actin assembly and membrane protrusion at the leading edge. 相似文献
50.