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81.
Mutations in a new photoreceptor-pineal gene on 17p cause Leber congenital amaurosis 总被引:6,自引:0,他引:6
Sohocki MM Bowne SJ Sullivan LS Blackshaw S Cepko CL Payne AM Bhattacharya SS Khaliq S Qasim Mehdi S Birch DG Harrison WR Elder FF Heckenlively JR Daiger SP 《Nature genetics》2000,24(1):79-83
Leber congenital amaurosis (LCA, MIM 204000) accounts for at least 5% of all inherited retinal disease and is the most severe inherited retinopathy with the earliest age of onset. Individuals affected with LCA are diagnosed at birth or in the first few months of life with severely impaired vision or blindness, nystagmus and an abnormal or flat electroretinogram (ERG). Mutations in GUCY2D (ref. 3), RPE65 (ref. 4) and CRX (ref. 5) are known to cause LCA, but one study identified disease-causing GUCY2D mutations in only 8 of 15 families whose LCA locus maps to 17p13.1 (ref. 3), suggesting another LCA locus might be located on 17p13.1. Confirming this prediction, the LCA in one Pakistani family mapped to 17p13.1, between D17S849 and D17S960-a region that excludes GUCY2D. The LCA in this family has been designated LCA4 (ref. 6). We describe here a new photoreceptor/pineal-expressed gene, AIPL1 (encoding aryl-hydrocarbon interacting protein-like 1), that maps within the LCA4 candidate region and whose protein contains three tetratricopeptide (TPR) motifs, consistent with nuclear transport or chaperone activity. A homozygous nonsense mutation at codon 278 is present in all affected members of the original LCA4 family. AIPL1 mutations may cause approximately 20% of recessive LCA, as disease-causing mutations were identified in 3 of 14 LCA families not tested previously for linkage. 相似文献
82.
TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease 总被引:120,自引:0,他引:120
Gross JA Johnston J Mudri S Enselman R Dillon SR Madden K Xu W Parrish-Novak J Foster D Lofton-Day C Moore M Littau A Grossman A Haugen H Foley K Blumberg H Harrison K Kindsvogel W Clegg CH 《Nature》2000,404(6781):995-999
B cells are important in the development of autoimmune disorders by mechanisms involving dysregulated polyclonal B-cell activation, production of pathogenic antibodies, and co-stimulation of autoreactive T cells. zTNF4 (BLyS, BAFF, TALL-1, THANK) is a member of the tumour necrosis factor (TNF) ligand family that is a potent co-activator of B cells in vitro and in vivo. Here we identify two receptors for zTNF4 and demonstrate a relationship between zTNF4 and autoimmune disease. Transgenic animals overexpressing zTNF4 in lymphoid cells develop symptoms characteristic of systemic lupus erythaematosus (SLE) and expand a rare population of splenic B-Ia lymphocytes. In addition, circulating zTNF4 is more abundant in NZBWF1 and MRL-lpr/lpr mice during the onset and progression of SLE. We have identified two TNF receptor family members, TACI and BCMA, that bind zTNF4. Treatment of NZBWF1 mice with soluble TACI-Ig fusion protein inhibits the development of proteinuria and prolongs survival of the animals. These findings demonstrate the involvement of zTNF4 and its receptors in the development of SLE and identify TACI-Ig as a promising treatment of autoimmune disease in humans. 相似文献
83.
Greenman C Stephens P Smith R Dalgliesh GL Hunter C Bignell G Davies H Teague J Butler A Stevens C Edkins S O'Meara S Vastrik I Schmidt EE Avis T Barthorpe S Bhamra G Buck G Choudhury B Clements J Cole J Dicks E Forbes S Gray K Halliday K Harrison R Hills K Hinton J Jenkinson A Jones D Menzies A Mironenko T Perry J Raine K Richardson D Shepherd R Small A Tofts C Varian J Webb T West S Widaa S Yates A Cahill DP Louis DN Goldstraw P Nicholson AG Brasseur F Looijenga L Weber BL Chiew YE DeFazio A 《Nature》2007,446(7132):153-158
Cancers arise owing to mutations in a subset of genes that confer growth advantage. The availability of the human genome sequence led us to propose that systematic resequencing of cancer genomes for mutations would lead to the discovery of many additional cancer genes. Here we report more than 1,000 somatic mutations found in 274 megabases (Mb) of DNA corresponding to the coding exons of 518 protein kinase genes in 210 diverse human cancers. There was substantial variation in the number and pattern of mutations in individual cancers reflecting different exposures, DNA repair defects and cellular origins. Most somatic mutations are likely to be 'passengers' that do not contribute to oncogenesis. However, there was evidence for 'driver' mutations contributing to the development of the cancers studied in approximately 120 genes. Systematic sequencing of cancer genomes therefore reveals the evolutionary diversity of cancers and implicates a larger repertoire of cancer genes than previously anticipated. 相似文献
84.
85.
Gal-Yam A Fox DB Price PA Ofek EO Davis MR Leonard DC Soderberg AM Schmidt BP Lewis KM Peterson BA Kulkarni SR Berger E Cenko SB Sari R Sharon K Frail D Moon DS Brown PJ Cucchiara A Harrison F Piran T Persson SE McCarthy PJ Penprase BE Chevalier RA MacFadyen AI 《Nature》2006,444(7122):1053-1055
Over the past decade, our physical understanding of gamma-ray bursts (GRBs) has progressed rapidly, thanks to the discovery and observation of their long-lived afterglow emission. Long-duration (> 2 s) GRBs are associated with the explosive deaths of massive stars ('collapsars', ref. 1), which produce accompanying supernovae; the short-duration (< or = 2 s) GRBs have a different origin, which has been argued to be the merger of two compact objects. Here we report optical observations of GRB 060614 (duration approximately 100 s, ref. 10) that rule out the presence of an associated supernova. This would seem to require a new explosive process: either a massive collapsar that powers a GRB without any associated supernova, or a new type of 'engine', as long-lived as the collapsar but without a massive star. We also show that the properties of the host galaxy (redshift z = 0.125) distinguish it from other long-duration GRB hosts and suggest that an entirely new type of GRB progenitor may be required. 相似文献
86.
WF Laurance DC Useche J Rendeiro M Kalka CJ Bradshaw SP Sloan SG Laurance M Campbell K Abernethy P Alvarez V Arroyo-Rodriguez P Ashton J Benítez-Malvido A Blom KS Bobo CH Cannon M Cao R Carroll C Chapman R Coates M Cords F Danielsen B De Dijn E Dinerstein MA Donnelly D Edwards F Edwards N Farwig P Fashing PM Forget M Foster G Gale D Harris R Harrison J Hart S Karpanty WJ Kress J Krishnaswamy W Logsdon J Lovett W Magnusson F Maisels AR Marshall D McClearn D Mudappa MR Nielsen R Pearson N Pitman 《Nature》2012,489(7415):290-294
The rapid disruption of tropical forests probably imperils global biodiversity more than any other contemporary phenomenon. With deforestation advancing quickly, protected areas are increasingly becoming final refuges for threatened species and natural ecosystem processes. However, many protected areas in the tropics are themselves vulnerable to human encroachment and other environmental stresses. As pressures mount, it is vital to know whether existing reserves can sustain their biodiversity. A critical constraint in addressing this question has been that data describing a broad array of biodiversity groups have been unavailable for a sufficiently large and representative sample of reserves. Here we present a uniquely comprehensive data set on changes over the past 20 to 30 years in 31 functional groups of species and 21 potential drivers of environmental change, for 60 protected areas stratified across the world’s major tropical regions. Our analysis reveals great variation in reserve ‘health’: about half of all reserves have been effective or performed passably, but the rest are experiencing an erosion of biodiversity that is often alarmingly widespread taxonomically and functionally. Habitat disruption, hunting and forest-product exploitation were the strongest predictors of declining reserve health. Crucially, environmental changes immediately outside reserves seemed nearly as important as those inside in determining their ecological fate, with changes inside reserves strongly mirroring those occurring around them. These findings suggest that tropical protected areas are often intimately linked ecologically to their surrounding habitats, and that a failure to stem broad-scale loss and degradation of such habitats could sharply increase the likelihood of serious biodiversity declines. 相似文献
87.
In recent years, considerable attention has focused on modelling and forecasting stock market volatility. Stock market volatility matters because stock markets are an integral part of the financial architecture in market economies and play a key role in channelling funds from savers to investors. The focus of this paper is on forecasting stock market volatility in Central and East European (CEE) countries. The obvious question to pose, therefore, is how volatility can be forecast and whether one technique consistently outperforms other techniques. Over the years a variety of techniques have been developed, ranging from the relatively simple to the more complex conditional heteroscedastic models of the GARCH family. In this paper we test the predictive power of 12 models to forecast volatility in the CEE countries. Our results confirm that models which allow for asymmetric volatility consistently outperform all other models considered. Copyright © 2011 John Wiley & Sons, Ltd. 相似文献
88.
Studies of the in vivo metabolism of 10,11-dihydrodibenz[b,f]-1,4-oxazepin-11-(1OH)-one (2) specifically deuteriated at C7 implicate an arene oxide intermediate during the conversion to 7-hydroxy-2 (4) as evidenced by the observation of the NIH shift. 相似文献
89.
Pattern of remyelination in the CNS 总被引:3,自引:0,他引:3
90.
J. M. Harrison R. J. Clarke T. D. Inch D. G. Upshall 《Cellular and molecular life sciences : CMLS》1978,34(6):698-699
Summary Studies of the in vivo metabolism of 10,11-dihydrodibenz[b,f]-1,4-oxazepin-11-(1OH)-one (2) specifically deuteriated at C-7 implicate an arene oxide intermediate during the conversion to 7-hydroxy-2 (4) as evidenced by the observation of the NIH shift. 相似文献