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排序方式: 共有610条查询结果,搜索用时 93 毫秒
111.
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113.
Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. 总被引:60,自引:0,他引:60
Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by a paucity of adipose (fat) tissue which is evident at birth and is accompanied by a severe resistance to insulin, leading to hyperinsulinaemia, hyperglycaemia and enlarged fatty liver. We have developed a mouse model that mimics these features of CGL: the syndrome occurs in transgenic mice expressing a truncated version of a nuclear protein known as nSREBP-1c (for sterol-regulatory-element-binding protein-1c) under the control of the adipose-specific aP2 enhancer. Adipose tissue from these mice was markedly deficient in messenger RNAs encoding several fat-specific proteins, including leptin, a fat-derived hormone that regulates food intake and energy metabolism. Here we show that insulin resistance in our lipodystrophic mice can be overcome by a continuous systemic infusion of low doses of recombinant leptin, an effect that is not mimicked by chronic food restriction. Our results support the idea that leptin modulates insulin sensitivity and glucose disposal independently of its effect on food intake, and that leptin deficiency accounts for the insulin resistance found in CGL. 相似文献
114.
We have calculated two new sets of weights applicable to the General Household Survey (GHS) from 1979 to 2007. One of these is for use with any general analysis of GHS topics and the second is designed for analyses of data collected in the Family Information section. The methods used follow closely those employed by ONS from 1996 onwards. The performance of the weights is assessed in estimating the Total Fertility Rate (TFR) from 1971-2007, an aggregate measure of fertility for which reliable figures are available at national level from vital registration statistics. Our weights improve the GHS estimates, reducing bias both in the TFR and in age-specific fertility rates. 相似文献
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116.
Bentley DR Balasubramanian S Swerdlow HP Smith GP Milton J Brown CG Hall KP Evers DJ Barnes CL Bignell HR Boutell JM Bryant J Carter RJ Keira Cheetham R Cox AJ Ellis DJ Flatbush MR Gormley NA Humphray SJ Irving LJ Karbelashvili MS Kirk SM Li H Liu X Maisinger KS Murray LJ Obradovic B Ost T Parkinson ML Pratt MR Rasolonjatovo IM Reed MT Rigatti R Rodighiero C Ross MT Sabot A Sankar SV Scally A Schroth GP Smith ME Smith VP Spiridou A Torrance PE Tzonev SS Vermaas EH Walter K Wu X Zhang L Alam MD 《Nature》2008,456(7218):53-59
DNA sequence information underpins genetic research, enabling discoveries of important biological or medical benefit. Sequencing projects have traditionally used long (400-800 base pair) reads, but the existence of reference sequences for the human and many other genomes makes it possible to develop new, fast approaches to re-sequencing, whereby shorter reads are compared to a reference to identify intraspecies genetic variation. Here we report an approach that generates several billion bases of accurate nucleotide sequence per experiment at low cost. Single molecules of DNA are attached to a flat surface, amplified in situ and used as templates for synthetic sequencing with fluorescent reversible terminator deoxyribonucleotides. Images of the surface are analysed to generate high-quality sequence. We demonstrate application of this approach to human genome sequencing on flow-sorted X chromosomes and then scale the approach to determine the genome sequence of a male Yoruba from Ibadan, Nigeria. We build an accurate consensus sequence from >30x average depth of paired 35-base reads. We characterize four million single-nucleotide polymorphisms and four hundred thousand structural variants, many of which were previously unknown. Our approach is effective for accurate, rapid and economical whole-genome re-sequencing and many other biomedical applications. 相似文献
117.
The genome sequence of the rice blast fungus Magnaporthe grisea 总被引:8,自引:0,他引:8
Dean RA Talbot NJ Ebbole DJ Farman ML Mitchell TK Orbach MJ Thon M Kulkarni R Xu JR Pan H Read ND Lee YH Carbone I Brown D Oh YY Donofrio N Jeong JS Soanes DM Djonovic S Kolomiets E Rehmeyer C Li W Harding M Kim S Lebrun MH Bohnert H Coughlan S Butler J Calvo S Ma LJ Nicol R Purcell S Nusbaum C Galagan JE Birren BW 《Nature》2005,434(7036):980-986
Magnaporthe grisea is the most destructive pathogen of rice worldwide and the principal model organism for elucidating the molecular basis of fungal disease of plants. Here, we report the draft sequence of the M. grisea genome. Analysis of the gene set provides an insight into the adaptations required by a fungus to cause disease. The genome encodes a large and diverse set of secreted proteins, including those defined by unusual carbohydrate-binding domains. This fungus also possesses an expanded family of G-protein-coupled receptors, several new virulence-associated genes and large suites of enzymes involved in secondary metabolism. Consistent with a role in fungal pathogenesis, the expression of several of these genes is upregulated during the early stages of infection-related development. The M. grisea genome has been subject to invasion and proliferation of active transposable elements, reflecting the clonal nature of this fungus imposed by widespread rice cultivation. 相似文献
118.
A general model for ontogenetic growth. 总被引:36,自引:0,他引:36
Several equations have been proposed to describe ontogenetic growth trajectories for organisms justified primarily on the goodness of fit rather than on any biological mechanism. Here, we derive a general quantitative model based on fundamental principles for the allocation of metabolic energy between maintenance of existing tissue and the production of new biomass. We thus predict the parameters governing growth curves from basic cellular properties and derive a single parameterless universal curve that describes the growth of many diverse species. The model provides the basis for deriving allometric relationships for growth rates and the timing of life history events. 相似文献
119.
Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. 总被引:165,自引:0,他引:165
A Goate M C Chartier-Harlin M Mullan J Brown F Crawford L Fidani L Giuffra A Haynes N Irving L James 《Nature》1991,349(6311):704-706
A locus segregating with familial Alzheimer's disease (AD) has been mapped to chromosome 21, close to the amyloid precursor protein (APP) gene. Recombinants between the APP gene and the AD locus have been reported which seemed to exclude it as the site of the mutation causing familial AD. But recent genetic analysis of a large number of AD families has demonstrated that the disease is heterogeneous. Families with late-onset AD do not show linkage to chromosome 21 markers. Some families with early-onset AD show linkage to chromosome 21 markers, but some do not. This has led to the suggestion that there is non-allelic genetic heterogeneity even within early onset familial AD. To avoid the problems that heterogeneity poses for genetic analysis, we have examined the cosegregation of AD and markers along the long arm of chromosome 21 in a single family with AD confirmed by autopsy. Here we demonstrate that in this kindred, which shows linkage to chromosome 21 markers, there is a point mutation in the APP gene. This mutation causes an amino-acid substitution (Val----Ile) close to the carboxy terminus of the beta-amyloid peptide. Screening other cases of familial AD revealed a second unrelated family in which this variant occurs. This suggests that some cases of AD could be caused by mutations in the APP gene. 相似文献
120.
J. W. Brown A. D. Okonmah K. F. A. Soliman A. Carballeira L. M. Fishman 《Cellular and molecular life sciences : CMLS》1988,44(10):898-900
Summary In the presence of ethanol, corticosterone and dexamethasone inhibit choline acetyltransferase and acetylcholinesterase activities in cultured fetal brain cells of the rat. These results suggest that corticosteroids may have an important influence on the activity of cholinergic enzymes in the fetal brain and may antagonize the effects of ethanol in this setting. 相似文献