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排序方式: 共有267条查询结果,搜索用时 15 毫秒
71.
Yun Hyun Huh So Hee Kim Kyoung-Hwun Chung Sena Oh Min-Sung Kwon Hyun-Woo Choi Sangmyung Rhee Je-Hwang Ryu Zee Yong Park Chang-Duk Jun Woo Keun Song 《Cellular and molecular life sciences : CMLS》2013,70(24):4841-4854
Membrane protrusions, like lamellipodia, and cell movement are dependent on actin dynamics, which are regulated by a variety of actin-binding proteins acting cooperatively to reorganize actin filaments. Here, we provide evidence that Swiprosin-1, a newly identified actin-binding protein, modulates lamellipodial dynamics by regulating the accessibility of F-actin to cofilin. Overexpression of Swiprosin-1 increased lamellipodia formation in B16F10 melanoma cells, whereas knockdown of Swiprosin-1 inhibited EGF-induced lamellipodia formation, and led to a loss of actin stress fibers at the leading edges of cells but not in the cell cortex. Swiprosin-1 strongly facilitated the formation of entangled or clustered F-actin, which remodeled the structural organization of actin filaments making them inaccessible to cofilin. EGF-induced phosphorylation of Swiprosin-1 at Ser183, a phosphorylation site newly identified using mass spectrometry, effectively inhibited clustering of actin filaments and permitted cofilin access to F-actin, resulting in actin depolymerization. Cells overexpressing a Swiprosin-1 phosphorylation-mimicking mutant or a phosphorylation-deficient mutant exhibited irregular membrane dynamics during the protrusion and retraction cycles of lamellipodia. Taken together, these findings suggest that dynamic exchange of Swiprosin-1 phosphorylation and dephosphorylation is a novel mechanism that regulates actin dynamics by modulating the pattern of cofilin activity at the leading edges of cells. 相似文献
72.
Kuroki Y Toyoda A Noguchi H Taylor TD Itoh T Kim DS Kim DW Choi SH Kim IC Choi HH Kim YS Satta Y Saitou N Yamada T Morishita S Hattori M Sakaki Y Park HS Fujiyama A 《Nature genetics》2006,38(2):158-167
The mammalian Y chromosome has unique characteristics compared with the autosomes or X chromosomes. Here we report the finished sequence of the chimpanzee Y chromosome (PTRY), including 271 kb of the Y-specific pseudoautosomal region 1 and 12.7 Mb of the male-specific region of the Y chromosome. Greater sequence divergence between the human Y chromosome (HSAY) and PTRY (1.78%) than between their respective whole genomes (1.23%) confirmed the accelerated evolutionary rate of the Y chromosome. Each of the 19 PTRY protein-coding genes analyzed had at least one nonsynonymous substitution, and 11 genes had higher nonsynonymous substitution rates than synonymous ones, suggesting relaxation of selective constraint, positive selection or both. We also identified lineage-specific changes, including deletion of a 200-kb fragment from the pericentromeric region of HSAY, expansion of young Alu families in HSAY and accumulation of young L1 elements and long terminal repeat retrotransposons in PTRY. Reconstruction of the common ancestral Y chromosome reflects the dynamic changes in our genomes in the 5-6 million years since speciation. 相似文献
73.
Large-scale genome-wide association studies in East Asians identify new genetic loci influencing metabolic traits 总被引:1,自引:0,他引:1
Kim YJ Go MJ Hu C Hong CB Kim YK Lee JY Hwang JY Oh JH Kim DJ Kim NH Kim S Hong EJ Kim JH Min H Kim Y Zhang R Jia W Okada Y Takahashi A Kubo M Tanaka T Kamatani N Matsuda K;MAGIC consortium Park T Oh B Kimm K Kang D Shin C Cho NH Kim HL Han BG Lee JY Cho YS 《Nature genetics》2011,43(10):990-995
To identify the genetic bases for nine metabolic traits, we conducted a meta-analysis combining Korean genome-wide association results from the KARE project (n = 8,842) and the HEXA shared control study (n = 3,703). We verified the associations of the loci selected from the discovery meta-analysis in the replication stage (30,395 individuals from the BioBank Japan genome-wide association study and individuals comprising the Health2 and Shanghai Jiao Tong University Diabetes cohorts). We identified ten genome-wide significant signals newly associated with traits from an overall meta-analysis. The most compelling associations involved 12q24.11 (near MYL2) and 12q24.13 (in C12orf51) for high-density lipoprotein cholesterol, 2p21 (near SIX2-SIX3) for fasting plasma glucose, 19q13.33 (in RPS11) and 6q22.33 (in RSPO3) for renal traits, and 12q24.11 (near MYL2), 12q24.13 (in C12orf51 and near OAS1), 4q31.22 (in ZNF827) and 7q11.23 (near TBL2-BCL7B) for hepatic traits. These findings highlight previously unknown biological pathways for metabolic traits investigated in this study. 相似文献
74.
Park CC Ahn S Bloom JS Lin A Wang RT Wu T Sekar A Khan AH Farr CJ Lusis AJ Leahy RM Lange K Smith DJ 《Nature genetics》2008,40(4):421-429
We mapped regulatory loci for nearly all protein-coding genes in mammals using comparative genomic hybridization and expression array measurements from a panel of mouse-hamster radiation hybrid cell lines. The large number of breaks in the mouse chromosomes and the dense genotyping of the panel allowed extremely sharp mapping of loci. As the regulatory loci result from extra gene dosage, we call them copy number expression quantitative trait loci, or ceQTLs. The -2log10P support interval for the ceQTLs was <150 kb, containing an average of <2-3 genes. We identified 29,769 trans ceQTLs with -log10P > 4, including 13 hotspots each regulating >100 genes in trans. Further, this work identifies 2,761 trans ceQTLs harboring no known genes, and provides evidence for a mode of gene expression autoregulation specific to the X chromosome. 相似文献
75.
A new method and a supporting theorem for designing multiple-class piecewise linear classifiers are described. The method involves the cutting of straight line segments joining pairs of opposed points (i.e., points from distinct classes) ind-dimensional space. We refer to such straight line segments aslinks. We show how nearly to minimize the number of hyperplanes required to cut all of these links, thereby yielding a near-Bayes-optimal decision surface regardless of the number of classes, and we describe the underlying theory. This method does not require parameters to be specified by users — an improvement over earlier methods. Experiments on multiple-class data obtained from ship images show that classifiers designed by this method yield approximately the same error rate as the bestk-nearest neighbor rule, while providing faster decisions.This research was supported in part by the Army Research Office under grant DAAG29-84-K-0208 and in part by the University of California MICRO Program. We thank R. W. Doucette of the U.S. Naval Weapons Center and R. D. Holben of Ford Aerospace Corporation for providing the ship images in our experiments. 相似文献
76.
Fox DB Frail DA Price PA Kulkarni SR Berger E Piran T Soderberg AM Cenko SB Cameron PB Gal-Yam A Kasliwal MM Moon DS Harrison FA Nakar E Schmidt BP Penprase B Chevalier RA Kumar P Roth K Watson D Lee BL Shectman S Phillips MM Roth M McCarthy PJ Rauch M Cowie L Peterson BA Rich J Kawai N Aoki K Kosugi G Totani T Park HS MacFadyen A Hurley KC 《Nature》2005,437(7060):845-850
The final chapter in the long-standing mystery of the gamma-ray bursts (GRBs) centres on the origin of the short-hard class of bursts, which are suspected on theoretical grounds to result from the coalescence of neutron-star or black-hole binary systems. Numerous searches for the afterglows of short-hard bursts have been made, galvanized by the revolution in our understanding of long-duration GRBs that followed the discovery in 1997 of their broadband (X-ray, optical and radio) afterglow emission. Here we present the discovery of the X-ray afterglow of a short-hard burst, GRB 050709, whose accurate position allows us to associate it unambiguously with a star-forming galaxy at redshift z = 0.160, and whose optical lightcurve definitively excludes a supernova association. Together with results from three other recent short-hard bursts, this suggests that short-hard bursts release much less energy than the long-duration GRBs. Models requiring young stellar populations, such as magnetars and collapsars, are ruled out, while coalescing degenerate binaries remain the most promising progenitor candidates. 相似文献
77.
Um JY Jeong HJ Park RK Hong SH Kim HM 《Cellular and molecular life sciences : CMLS》2005,62(7-8):824-833
During the last decade, a growing corpus of evidence has indicated an important role of inflammatory cytokines in the pathogenesis of cerebral lesion following stroke. Recent data suggest that genetics may in turn contribute to modulating the effects of inflammatory cytokines on cerebral infarction (CI). This paper reviews the physiologic characteristics of major inflammatory cytokines and recent research developments related to cell biology and pathobiology in CI. In particular, this review focuses on the genetic aspects of inflammatory cytokines and their implications in CI.Received 22 June 2004; received after revision 11 November 2004; accepted 16 December 2004 相似文献
78.
79.
Sipa1 is a candidate for underlying the metastasis efficiency modifier locus Mtes1 总被引:10,自引:0,他引:10
Park YG Zhao X Lesueur F Lowy DR Lancaster M Pharoah P Qian X Hunter KW 《Nature genetics》2005,37(10):1055-1062
We previously identified loci in the mouse genome that substantially influence the metastatic efficiency of mammary tumors. Here, we present data supporting the idea that the signal transduction molecule, Sipa1, is a candidate for underlying the metastasis efficiency modifier locus Mtes1. Analysis of candidate genes identified a nonsynonymous amino acid polymorphism in Sipa1 that affects the Sipa1 Rap-GAP function. Spontaneous metastasis assays using cells ectopically expressing Sipa1 or cells with knocked-down Sipa1 expression showed that metastatic capacity was correlated with cellular Sipa1 levels. We examined human expression data and found that they were consistent with the idea that Sipa1 concentration has a role in metastasis. Taken together, these data suggest that the Sipa1 polymorphism is one of the genetic polymorphisms underlying the Mtes1 locus. This report is also the first demonstration, to our knowledge, of a constitutional genetic polymorphism affecting tumor metastasis. 相似文献
80.
Choi MH Lee IK Kim GW Kim BU Han YH Yu DY Park HS Kim KY Lee JS Choi C Bae YS Lee BI Rhee SG Kang SW 《Nature》2005,435(7040):347-353
Platelet-derived growth factor (PDGF) is a potent mitogenic and migratory factor that regulates the tyrosine phosphorylation of a variety of signalling proteins via intracellular production of H2O2 (refs 1, 2-3). Mammalian 2-Cys peroxiredoxin type II (Prx II; gene symbol Prdx2) is a cellular peroxidase that eliminates endogenous H2O2 produced in response to growth factors such as PDGF and epidermal growth factor; however, its involvement in growth factor signalling is largely unknown. Here we show that Prx II is a negative regulator of PDGF signalling. Prx II deficiency results in increased production of H2O2, enhanced activation of PDGF receptor (PDGFR) and phospholipase Cgamma1, and subsequently increased cell proliferation and migration in response to PDGF. These responses are suppressed by expression of wild-type Prx II, but not an inactive mutant. Notably, Prx II is recruited to PDGFR upon PDGF stimulation, and suppresses protein tyrosine phosphatase inactivation. Prx II also leads to the suppression of PDGFR activation in primary culture and a murine restenosis model, including PDGF-dependent neointimal thickening of vascular smooth muscle cells. These results demonstrate a localized role for endogenous H2O2 in PDGF signalling, and indicate a biological function of Prx II in cardiovascular disease. 相似文献