全文获取类型
收费全文 | 17294篇 |
免费 | 26篇 |
国内免费 | 67篇 |
专业分类
系统科学 | 123篇 |
丛书文集 | 288篇 |
教育与普及 | 43篇 |
理论与方法论 | 64篇 |
现状及发展 | 7415篇 |
研究方法 | 909篇 |
综合类 | 8282篇 |
自然研究 | 263篇 |
出版年
2013年 | 113篇 |
2012年 | 301篇 |
2011年 | 567篇 |
2010年 | 105篇 |
2009年 | 100篇 |
2008年 | 316篇 |
2007年 | 361篇 |
2006年 | 378篇 |
2005年 | 376篇 |
2004年 | 378篇 |
2003年 | 324篇 |
2002年 | 321篇 |
2001年 | 609篇 |
2000年 | 571篇 |
1999年 | 389篇 |
1992年 | 326篇 |
1991年 | 264篇 |
1990年 | 279篇 |
1989年 | 253篇 |
1988年 | 235篇 |
1987年 | 281篇 |
1986年 | 292篇 |
1985年 | 320篇 |
1984年 | 280篇 |
1983年 | 222篇 |
1982年 | 182篇 |
1981年 | 195篇 |
1980年 | 249篇 |
1979年 | 566篇 |
1978年 | 432篇 |
1977年 | 425篇 |
1976年 | 314篇 |
1975年 | 350篇 |
1974年 | 517篇 |
1973年 | 437篇 |
1972年 | 428篇 |
1971年 | 519篇 |
1970年 | 690篇 |
1969年 | 484篇 |
1968年 | 401篇 |
1967年 | 489篇 |
1966年 | 398篇 |
1965年 | 282篇 |
1959年 | 163篇 |
1958年 | 268篇 |
1957年 | 207篇 |
1956年 | 180篇 |
1955年 | 145篇 |
1954年 | 150篇 |
1948年 | 126篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
981.
982.
Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration 总被引:23,自引:0,他引:23
Lin SJ Kaeberlein M Andalis AA Sturtz LA Defossez PA Culotta VC Fink GR Guarente L 《Nature》2002,418(6895):344-348
Calorie restriction (CR) extends lifespan in a wide spectrum of organisms and is the only regimen known to lengthen the lifespan of mammals. We established a model of CR in budding yeast Saccharomyces cerevisiae. In this system, lifespan can be extended by limiting glucose or by reducing the activity of the glucose-sensing cyclic-AMP-dependent kinase (PKA). Lifespan extension in a mutant with reduced PKA activity requires Sir2 and NAD (nicotinamide adenine dinucleotide). In this study we explore how CR activates Sir2 to extend lifespan. Here we show that the shunting of carbon metabolism toward the mitochondrial tricarboxylic acid cycle and the concomitant increase in respiration play a central part in this process. We discuss how this metabolic strategy may apply to CR in animals. 相似文献
983.
984.
The parathyroid hormone 1 receptor (PTH1R) is a class II G-protein-coupled receptor. PTH1R agonists include both PTH, a hormone that regulates blood calcium and phosphate, and PTH-related protein (PTHrP), a paracrine/autocrine factor that is essential for development, particularly of the skeleton. Adenylyl cyclase activation is thought to be responsible for most cellular responses to PTH and PTHrP, although many actions appear to be independent of adenylyl cyclase. Here we show that the PTH1R binds to Na(+)/H(+) exchanger regulatory factors (NHERF) 1 and 2 through a PDZ-domain interaction in vitro and in PTH target cells. NHERF2 simultaneously binds phospholipase C beta 1 and an atypical, carboxyl-terminal PDZ consensus motif, ETVM, of the PTH1R through PDZ1 and PDZ2, respectively. PTH treatment of cells that express the NHERF2 PTH1R complex markedly activates phospholipase C beta and inhibits adenylyl cyclase through stimulation of inhibitory G proteins (G(i/o) proteins). NHERF-mediated assembly of PTH1R and phospholipase C beta is a unique mechanism to regulate PTH signalling in cells and membranes of polarized cells that express NHERF, which may account for many tissue- and cell-specific actions of PTH/PTHrP and may also be relevant to signalling by many G-protein-coupled receptors. 相似文献
985.
986.
Coulomb blockade and the Kondo effect in single-atom transistors 总被引:7,自引:0,他引:7
Park J Pasupathy AN Goldsmith JI Chang C Yaish Y Petta JR Rinkoski M Sethna JP Abruña HD McEuen PL Ralph DC 《Nature》2002,417(6890):722-725
Using molecules as electronic components is a powerful new direction in the science and technology of nanometre-scale systems. Experiments to date have examined a multitude of molecules conducting in parallel, or, in some cases, transport through single molecules. The latter includes molecules probed in a two-terminal geometry using mechanically controlled break junctions or scanning probes as well as three-terminal single-molecule transistors made from carbon nanotubes, C(60) molecules, and conjugated molecules diluted in a less-conducting molecular layer. The ultimate limit would be a device where electrons hop on to, and off from, a single atom between two contacts. Here we describe transistors incorporating a transition-metal complex designed so that electron transport occurs through well-defined charge states of a single atom. We examine two related molecules containing a Co ion bonded to polypyridyl ligands, attached to insulating tethers of different lengths. Changing the length of the insulating tether alters the coupling of the ion to the electrodes, enabling the fabrication of devices that exhibit either single-electron phenomena, such as Coulomb blockade, or the Kondo effect. 相似文献
987.
VEGF regulates haematopoietic stem cell survival by an internal autocrine loop mechanism 总被引:49,自引:0,他引:49
Gerber HP Malik AK Solar GP Sherman D Liang XH Meng G Hong K Marsters JC Ferrara N 《Nature》2002,417(6892):954-958
Vascular endothelial growth factor (VEGF) is a principal regulator of blood vessel formation and haematopoiesis, but the mechanisms by which VEGF differentially regulates these processes have been elusive. Here we describe a regulatory loop by which VEGF controls survival of haematopoietic stem cells (HSCs). We observed a reduction in survival, colony formation and in vivo repopulation rates of HSCs after ablation of the VEGF gene in mice. Intracellularly acting small-molecule inhibitors of VEGF receptor (VEGFR) tyrosine kinase dramatically reduced colony formation of HSCs, thus mimicking deletion of the VEGF gene. However, blocking VEGF by administering a soluble VEGFR-1, which acts extracellularly, induced only minor effects. These findings support the involvement in HSC survival of a VEGF-dependent internal autocrine loop mechanism (that is, the mechanism is resistant to inhibitors that fail to penetrate the intracellular compartment). Not only ligands selective for VEGF and VEGFR-2 but also VEGFR-1 agonists rescued survival and repopulation of VEGF-deficient HSCs, revealing a function for VEGFR-1 signalling during haematopoiesis. 相似文献
988.
Widespread use of antimalarial agents can profoundly influence the evolution of the human malaria parasite Plasmodium falciparum. Recent selective sweeps for drug-resistant genotypes may have restricted the genetic diversity of this parasite, resembling effects attributed in current debates to a historic population bottleneck. Chloroquine-resistant (CQR) parasites were initially reported about 45 years ago from two foci in southeast Asia and South America, but the number of CQR founder mutations and the impact of chlorquine on parasite genomes worldwide have been difficult to evaluate. Using 342 highly polymorphic microsatellite markers from a genetic map, here we show that the level of genetic diversity varies substantially among different regions of the parasite genome, revealing extensive linkage disequilibrium surrounding the key CQR gene pfcrt and at least four CQR founder events. This disequilibrium and its decay rate in the pfcrt-flanking region are consistent with strong directional selective sweeps occurring over only approximately 20-80 sexual generations, especially a single resistant pfcrt haplotype spreading to very high frequencies throughout most of Asia and Africa. The presence of linkage disequilibrium provides a basis for mapping genes under drug selection in P. falciparum. 相似文献
989.
Genetic analysis of the mouse brain proteome 总被引:24,自引:0,他引:24
Klose J Nock C Herrmann M Stühler K Marcus K Blüggel M Krause E Schalkwyk LC Rastan S Brown SD Büssow K Himmelbauer H Lehrach H 《Nature genetics》2002,30(4):385-393
Proteome analysis is a fundamental step in systematic functional genomics. Here we have resolved 8,767 proteins from the mouse brain proteome by large-gel two-dimensional electrophoresis. We detected 1,324 polymorphic proteins from the European collaborative interspecific backcross. Of these, we mapped 665 proteins genetically and identified 466 proteins by mass spectrometry. Qualitatively polymorphic proteins, to 96%, reflect changes in conformation and/or mass. Quantitatively polymorphic proteins show a high frequency (73%) of allele-specific transmission in codominant heterozygotes. Variations in protein isoforms and protein quantity often mapped to chromosomal positions different from that of the structural gene, indicating that single proteins may act as polygenic traits. Genetic analysis of proteomes may detect the types of polymorphism that are most relevant in disease-association studies. 相似文献
990.
Cyclin A in cell cycle control and cancer 总被引:16,自引:0,他引:16