全文获取类型
收费全文 | 16830篇 |
免费 | 97篇 |
国内免费 | 90篇 |
专业分类
系统科学 | 69篇 |
丛书文集 | 137篇 |
教育与普及 | 41篇 |
理论与方法论 | 41篇 |
现状及发展 | 6993篇 |
研究方法 | 807篇 |
综合类 | 8684篇 |
自然研究 | 245篇 |
出版年
2012年 | 235篇 |
2011年 | 494篇 |
2010年 | 107篇 |
2009年 | 102篇 |
2008年 | 292篇 |
2007年 | 356篇 |
2006年 | 301篇 |
2005年 | 320篇 |
2004年 | 419篇 |
2003年 | 291篇 |
2002年 | 307篇 |
2001年 | 638篇 |
2000年 | 647篇 |
1999年 | 456篇 |
1994年 | 300篇 |
1992年 | 345篇 |
1991年 | 303篇 |
1990年 | 317篇 |
1989年 | 276篇 |
1988年 | 268篇 |
1987年 | 291篇 |
1986年 | 300篇 |
1985年 | 390篇 |
1984年 | 297篇 |
1983年 | 246篇 |
1982年 | 212篇 |
1981年 | 236篇 |
1980年 | 239篇 |
1979年 | 543篇 |
1978年 | 441篇 |
1977年 | 378篇 |
1976年 | 321篇 |
1975年 | 336篇 |
1974年 | 403篇 |
1973年 | 332篇 |
1972年 | 375篇 |
1971年 | 436篇 |
1970年 | 547篇 |
1969年 | 427篇 |
1968年 | 396篇 |
1967年 | 396篇 |
1966年 | 395篇 |
1965年 | 285篇 |
1959年 | 121篇 |
1958年 | 224篇 |
1957年 | 156篇 |
1956年 | 129篇 |
1955年 | 101篇 |
1954年 | 130篇 |
1948年 | 103篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Hermann H De Petrocellis L Bisogno T Schiano Moriello A Lutz B Di Marzo V 《Cellular and molecular life sciences : CMLS》2003,60(3):607-616
Cannabinoid CB1 receptors and vanilloid VR1 receptors are co-localized to some extent in sensory neurons of the spinal cord and dorsal root ganglia. In this study, we over-expressed both receptor types in human embryonic kidney (HEK)-293 cells and investigated the effect of the CB1 agonist HU-210 on the VR1-mediated increase in intracellular Ca2+ ([Ca2+]i), a well-known response of the prototypical VR1 agonist capsaicin. After a 5-min pre-treatment, HU-210 (0.1 microM) significantly enhanced the effect of several concentrations of capsaicin on [Ca2+]i in HEK-293 cells over-expressing both rat CB1 and human VR1 (CB1-VR1-HEK cells), but not in cells over-expressing only human VR1 (VR1-HEK cells). This effect was blocked by the CB1 receptor antagonist SR141716A (0.5 microM), and by phosphoinositide-3-kinase and phospholipase C inhibitors. The endogenous agonist of CB1 and VR1 receptors, anandamide, was more efficacious in inducing a VR1-mediated stimulation of [Ca2+]i in CB1-VR1-HEK cells than in VR1-HEK cells, and part of its effect on the former cells was blocked by SR141716A (0.5 microM). Pre-treatment of CB1-VR1-HEK cells with forskolin, an adenylate cyclase activator, enhanced the capsaicin effect on [Ca2+]i. HU-210, which in the same cells inhibits forskolin-induced enhancement of cAMP levels, blocked the stimulatory effect of forskolin on capsaicin. Our data suggest that in cells co-expressing both CB1 and VR1 receptors, pre-treatment with CB1 agonists inhibits or stimulates VR1 gating by capsaicin depending on whether or not cAMP-mediated signalling has been concomitantly activated. 相似文献
992.
993.
Understanding why some cellular components are conserved across species but others evolve rapidly is a key question of modern biology. Here we show that in Saccharomyces cerevisiae, proteins organized in cohesive patterns of interactions are conserved to a substantially higher degree than those that do not participate in such motifs. We find that the conservation of proteins in distinct topological motifs correlates with the interconnectedness and function of that motif and also depends on the structure of the overall interactome topology. These findings indicate that motifs may represent evolutionary conserved topological units of cellular networks molded in accordance with the specific biological function in which they participate. 相似文献
994.
The atmosphere of Jupiter's satellite Io is extremely tenuous, time variable and spatially heterogeneous. Only a few molecules--SO2, SO and S2--have previously been identified as constituents of this atmosphere, and possible sources include frost sublimation, surface sputtering and active volcanism. Io has been known for almost 30 years to be surrounded by a cloud of Na, which requires an as yet unidentified atmospheric source of sodium. Sodium chloride has been recently proposed as an important atmospheric constituent, based on the detection of chlorine in Io's plasma torus and models of Io's volcanic gases. Here we report the detection of NaCl in Io's atmosphere; it constitutes only approximately 0.3% when averaged over the entire disk, but is probably restricted to smaller regions than SO2 because of its rapid photolysis and surface condensation. Although the inferred abundance of NaCl in volcanic gases is lower than predicted, those volcanic emissions provide an important source of Na and Cl in Io's neutral clouds and plasma torus. 相似文献
995.
996.
997.
An epi-allelic series of p53 hypomorphs created by stable RNAi produces distinct tumor phenotypes in vivo 总被引:45,自引:0,他引:45
Hemann MT Fridman JS Zilfou JT Hernando E Paddison PJ Cordon-Cardo C Hannon GJ Lowe SW 《Nature genetics》2003,33(3):396-400
The application of RNA interference (RNAi) to mammalian systems has the potential to revolutionize genetics and produce novel therapies. Here we investigate whether RNAi applied to a well-characterized gene can stably suppress gene expression in hematopoietic stem cells and produce detectable phenotypes in mice. Deletion of the Trp53 tumor suppressor gene greatly accelerates Myc-induced lymphomagenesis, resulting in highly disseminated disease. To determine whether RNAi suppression of Trp53 could produce a similar phenotype, we introduced several Trp53 short hairpin RNAs (shRNAs) into hematopoietic stem cells derived from E(mu)-Myc transgenic mice, and monitored tumor onset and overall pathology in lethally irradiated recipients. Different Trp53 shRNAs produced distinct phenotypes in vivo, ranging from benign lymphoid hyperplasias to highly disseminated lymphomas that paralleled Trp53-/- lymphomagenesis in the E(mu)-Myc mouse. In all cases, the severity and type of disease correlated with the extent to which specific shRNAs inhibited p53 activity. Therefore, RNAi can stably suppress gene expression in stem cells and reconstituted organs derived from those cells. In addition, intrinsic differences between individual shRNA expression vectors targeting the same gene can be used to create an 'epi-allelic series' for dissecting gene function in vivo. 相似文献
998.
Regulatory defects in liver and intestine implicate abnormal hepcidin and Cybrd1 expression in mouse hemochromatosis 总被引:21,自引:0,他引:21
Muckenthaler M Roy CN Custodio AO Miñana B deGraaf J Montross LK Andrews NC Hentze MW 《Nature genetics》2003,34(1):102-107
Individuals with hereditary hemochromatosis suffer from systemic iron overload due to duodenal hyperabsorption. Most cases arise from a founder mutation in HFE (845G-->A; ref. 2) that results in the amino-acid substitution C282Y and prevents the association of HFE with beta2-microglobulin. Mice homozygous with respect to a null allele of Hfe (Hfe-/-) or homozygous with respect to the orthologous 882G-->A mutation (Hfe(845A/845A)) develop iron overload that recapitulates hereditary hemochromatosis in humans, confirming that hereditary hemochromatosis arises from loss of HFE function. Much work has focused on an exclusive role for the intestine in hereditary hemochromatosis. HFE deficiency in intestinal crypt cells is thought to cause intestinal iron deficiency and greater expression of iron transporters such as SLC11A2 (also called DMT1, DCT1 and NRAMP2) and SLC11A3 (also called IREG1, ferroportin and MTP1; ref. 3). Published data on the expression of these transporters in the duodenum of HFE-deficient mice and humans are contradictory. In this report, we used a custom microarray to assay changes in duodenal and hepatic gene expression in Hfe-deficient mice. We found unexpected alterations in the expression of Slc39a1 (mouse ortholog of SLC11A3) and Cybrd1, which encode key iron transport proteins, and Hamp (hepcidin antimicrobial peptide), a hepatic regulator of iron transport. We propose that inappropriate regulatory cues from the liver underlie greater duodenal iron absorption, possibly involving the ferric reductase Cybrd1. 相似文献
999.
Hypotrichosis simplex of the scalp is associated with nonsense mutations in CDSN encoding corneodesmosin 总被引:6,自引:0,他引:6
Levy-Nissenbaum E Betz RC Frydman M Simon M Lahat H Bakhan T Goldman B Bygum A Pierick M Hillmer AM Jonca N Toribio J Kruse R Dewald G Cichon S Kubisch C Guerrin M Serre G Nöthen MM Pras E 《Nature genetics》2003,34(2):151-153
We have identified nonsense mutations in the gene CDSN (encoding corneodesmosin) in three families suffering from hypotrichosis simplex of the scalp (HSS; OMIM 146520). CDSN, a glycoprotein expressed in the epidermis and inner root sheath (IRS) of hair follicles, is a keratinocyte adhesion molecule. Truncated CDSN aggregates were detected in the superficial dermis and at the periphery of hair follicles. Our findings suggest that CDSN is important in normal scalp hair physiology. 相似文献
1000.
Inada N Oguri M Pindor B Hennawi JF Chiu K Zheng W Ichikawa S Gregg MD Becker RH Suto Y Strauss MA Turner EL Keeton CR Annis J Castander FJ Eisenstein DJ Frieman JA Fukugita M Gunn JE Johnston DE Kent SM Nichol RC Richards GT Rix HW Sheldon ES Bahcall NA Brinkmann J Ivezić Z Lamb DQ McKay TA Schneider DP York DG 《Nature》2003,426(6968):810-812
Gravitational lensing is a powerful tool for the study of the distribution of dark matter in the Universe. The cold-dark-matter model of the formation of large-scale structures (that is, clusters of galaxies and even larger assemblies) predicts the existence of quasars gravitationally lensed by concentrations of dark matter so massive that the quasar images would be split by over 7 arcsec. Numerous searches for large-separation lensed quasars have, however, been unsuccessful. All of the roughly 70 lensed quasars known, including the first lensed quasar discovered, have smaller separations that can be explained in terms of galaxy-scale concentrations of baryonic matter. Although gravitationally lensed galaxies with large separations are known, quasars are more useful cosmological probes because of the simplicity of the resulting lens systems. Here we report the discovery of a lensed quasar, SDSS J1004 + 4112, which has a maximum separation between the components of 14.62 arcsec. Such a large separation means that the lensing object must be dominated by dark matter. Our results are fully consistent with theoretical expectations based on the cold-dark-matter model. 相似文献