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71.
72.
The discovery of the RNA self-splicing group I intron provided the first demonstration that not all enzymes are proteins. Here we report the X-ray crystal structure (3.1-A resolution) of a complete group I bacterial intron in complex with both the 5'- and the 3'-exons. This complex corresponds to the splicing intermediate before the exon ligation step. It reveals how the intron uses structurally unprecedented RNA motifs to select the 5'- and 3'-splice sites. The 5'-exon's 3'-OH is positioned for inline nucleophilic attack on the conformationally constrained scissile phosphate at the intron-3'-exon junction. Six phosphates from three disparate RNA strands converge to coordinate two metal ions that are asymmetrically positioned on opposing sides of the reactive phosphate. This structure represents the first splicing complex to include a complete intron, both exons and an organized active site occupied with metal ions. 相似文献
73.
Votier SC Furness RW Bearhop S Crane JE Caldow RW Catry P Ensor K Hamer KC Hudson AV Kalmbach E Klomp NI Pfeiffer S Phillips RA Prieto I Thompson DR 《Nature》2004,427(6976):727-730
It is clear that discards from commercial fisheries are a key food resource for many seabird species around the world. But predicting the response of seabird communities to changes in discard rates is problematic and requires historical data to elucidate the confounding effects of other, more 'natural' ecological processes. In the North Sea, declining stocks, changes in technical measures, changes in population structure and the establishment of a recovery programme for cod (Gadus morhua) will alter the amount of fish discarded. This region also supports internationally important populations of seabirds, some of which feed extensively, but facultatively, on discards, in particular on undersized haddock (Melanogrammus aeglefinus) and whiting (Merlangius merlangus). Here we use long-term data sets from the northern North Sea to show that there is a direct link between discard availability and discard use by a generalist predator and scavenger--the great skua (Stercorarius skua). Reduced rates of discarding, particularly when coupled with reduced availability of small shoaling pelagic fish such as sandeel (Ammodytes marinus), result in an increase in predation by great skuas on other birds. This switching of prey by a facultative scavenger presents a potentially serious threat to some seabird communities. 相似文献
74.
A 'snowball Earth' climate triggered by continental break-up through changes in runoff 总被引:1,自引:0,他引:1
Geological and palaeomagnetic studies indicate that ice sheets may have reached the Equator at the end of the Proterozoic eon, 800 to 550 million years ago, leading to the suggestion of a fully ice-covered 'snowball Earth'. Climate model simulations indicate that such a snowball state for the Earth depends on anomalously low atmospheric carbon dioxide concentrations, in addition to the Sun being 6 per cent fainter than it is today. However, the mechanisms producing such low carbon dioxide concentrations remain controversial. Here we assess the effect of the palaeogeographic changes preceding the Sturtian glacial period, 750 million years ago, on the long-term evolution of atmospheric carbon dioxide levels using the coupled climate-geochemical model GEOCLIM. In our simulation, the continental break-up of Rodinia leads to an increase in runoff and hence consumption of carbon dioxide through continental weathering that decreases atmospheric carbon dioxide concentrations by 1,320 p.p.m. This indicates that tectonic changes could have triggered a progressive transition from a 'greenhouse' to an 'icehouse' climate during the Neoproterozoic era. When we combine these results with the concomitant weathering effect of the voluminous basaltic traps erupted throughout the break-up of Rodinia, our simulation results in a snowball glaciation. 相似文献
75.
76.
Friml J Vieten A Sauer M Weijers D Schwarz H Hamann T Offringa R Jürgens G 《Nature》2003,426(6963):147-153
Axis formation occurs in plants, as in animals, during early embryogenesis. However, the underlying mechanism is not known. Here we show that the first manifestation of the apical-basal axis in plants, the asymmetric division of the zygote, produces a basal cell that transports and an apical cell that responds to the signalling molecule auxin. This apical-basal auxin activity gradient triggers the specification of apical embryo structures and is actively maintained by a novel component of auxin efflux, PIN7, which is located apically in the basal cell. Later, the developmentally regulated reversal of PIN7 and onset of PIN1 polar localization reorganize the auxin gradient for specification of the basal root pole. An analysis of pin quadruple mutants identifies PIN-dependent transport as an essential part of the mechanism for embryo axis formation. Our results indicate how the establishment of cell polarity, polar auxin efflux and local auxin response result in apical-basal axis formation of the embryo, and thus determine the axiality of the adult plant. 相似文献
77.
Howitz KT Bitterman KJ Cohen HY Lamming DW Lavu S Wood JG Zipkin RE Chung P Kisielewski A Zhang LL Scherer B Sinclair DA 《Nature》2003,425(6954):191-196
In diverse organisms, calorie restriction slows the pace of ageing and increases maximum lifespan. In the budding yeast Saccharomyces cerevisiae, calorie restriction extends lifespan by increasing the activity of Sir2 (ref. 1), a member of the conserved sirtuin family of NAD(+)-dependent protein deacetylases. Included in this family are SIR-2.1, a Caenorhabditis elegans enzyme that regulates lifespan, and SIRT1, a human deacetylase that promotes cell survival by negatively regulating the p53 tumour suppressor. Here we report the discovery of three classes of small molecules that activate sirtuins. We show that the potent activator resveratrol, a polyphenol found in red wine, lowers the Michaelis constant of SIRT1 for both the acetylated substrate and NAD(+), and increases cell survival by stimulating SIRT1-dependent deacetylation of p53. In yeast, resveratrol mimics calorie restriction by stimulating Sir2, increasing DNA stability and extending lifespan by 70%. We discuss possible evolutionary origins of this phenomenon and suggest new lines of research into the therapeutic use of sirtuin activators. 相似文献
78.
Reconstruction of gene association network reveals a transmembrane protein required for adipogenesis and targeted by PPARγ 总被引:1,自引:0,他引:1
Juliane G. Bogner-Strauss Andreas Prokesch Fatima Sanchez-Cabo Dietmar Rieder Hubert Hackl Kalina Duszka Anne Krogsdam Barbara Di Camillo Evelyn Walenta Ariane Klatzer Achim Lass Montserrat Pinent Wing-Cheong Wong Frank Eisenhaber Zlatko Trajanoski 《Cellular and molecular life sciences : CMLS》2010,67(23):4049-4064
79.
Speliotes EK Willer CJ Berndt SI Monda KL Thorleifsson G Jackson AU Lango Allen H Lindgren CM Luan J Mägi R Randall JC Vedantam S Winkler TW Qi L Workalemahu T Heid IM Steinthorsdottir V Stringham HM Weedon MN Wheeler E Wood AR Ferreira T Weyant RJ Segrè AV Estrada K Liang L Nemesh J Park JH Gustafsson S Kilpeläinen TO Yang J Bouatia-Naji N Esko T Feitosa MF Kutalik Z Mangino M Raychaudhuri S Scherag A Smith AV Welch R Zhao JH Aben KK Absher DM Amin N Dixon AL Fisher E Glazer NL Goddard ME 《Nature genetics》2010,42(11):937-948
Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10??), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation. 相似文献
80.
Coucke PJ Willaert A Wessels MW Callewaert B Zoppi N De Backer J Fox JE Mancini GM Kambouris M Gardella R Facchetti F Willems PJ Forsyth R Dietz HC Barlati S Colombi M Loeys B De Paepe A 《Nature genetics》2006,38(4):452-457
Arterial tortuosity syndrome (ATS) is an autosomal recessive disorder characterized by tortuosity, elongation, stenosis and aneurysm formation in the major arteries owing to disruption of elastic fibers in the medial layer of the arterial wall. Previously, we used homozygosity mapping to map a candidate locus in a 4.1-Mb region on chromosome 20q13.1 (ref. 2). Here, we narrowed the candidate region to 1.2 Mb containing seven genes. Mutations in one of these genes, SLC2A10, encoding the facilitative glucose transporter GLUT10, were identified in six ATS families. GLUT10 deficiency is associated with upregulation of the TGFbeta pathway in the arterial wall, a finding also observed in Loeys-Dietz syndrome, in which aortic aneurysms associate with arterial tortuosity. The identification of a glucose transporter gene responsible for altered arterial morphogenesis is notable in light of the previously suggested link between GLUT10 and type 2 diabetes. Our data could provide new insight on the mechanisms causing microangiopathic changes associated with diabetes and suggest that therapeutic compounds intervening with TGFbeta signaling represent a new treatment strategy. 相似文献