全文获取类型
收费全文 | 518篇 |
免费 | 6篇 |
国内免费 | 28篇 |
专业分类
系统科学 | 6篇 |
教育与普及 | 12篇 |
现状及发展 | 30篇 |
研究方法 | 113篇 |
综合类 | 391篇 |
出版年
2023年 | 2篇 |
2021年 | 2篇 |
2020年 | 1篇 |
2019年 | 4篇 |
2018年 | 6篇 |
2017年 | 3篇 |
2016年 | 2篇 |
2014年 | 7篇 |
2013年 | 3篇 |
2012年 | 55篇 |
2011年 | 58篇 |
2010年 | 10篇 |
2009年 | 5篇 |
2008年 | 37篇 |
2007年 | 57篇 |
2006年 | 47篇 |
2005年 | 55篇 |
2004年 | 29篇 |
2003年 | 45篇 |
2002年 | 31篇 |
2001年 | 31篇 |
2000年 | 35篇 |
1999年 | 6篇 |
1998年 | 1篇 |
1996年 | 2篇 |
1994年 | 1篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1979年 | 1篇 |
1970年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有552条查询结果,搜索用时 62 毫秒
2.
Existing home devices in home network provides only independent services limited on a homogeneous protocol and/or do not fully support an intelligent service provided by cooperating among heterogeneous protocol devices. This paper proposes an intelligent and integrated service binding architecture which allow the users to figure out the status of devices and to cooperate among home network devices regardless of supported protocols or operational characteristics. 相似文献
3.
近红外光谱技术分析速度快、效率高、成本低、重现性好,典型的无损分析;主要用于样品类别鉴定和纯度检验.近红外光谱技术结合模式识别方法,在纯品油种类的鉴别中已得到成功应用[1,2],本实验室也初步建立了纯品油近红外谱图数据库[3],但该法在实际海面溢油样品的鉴别中应用仍甚少. 相似文献
4.
通过对不同模具材料模塑的制件试样进行残余固化度和拉伸强度的测定,分析了RTM模具材料的传热特性对制件性能的影响。 相似文献
5.
Chiang C Jacobsen JC Ernst C Hanscom C Heilbut A Blumenthal I Mills RE Kirby A Lindgren AM Rudiger SR McLaughlan CJ Bawden CS Reid SJ Faull RL Snell RG Hall IM Shen Y Ohsumi TK Borowsky ML Daly MJ Lee C Morton CC MacDonald ME Gusella JF Talkowski ME 《Nature genetics》2012,44(4):390-7, S1
We defined the genetic landscape of balanced chromosomal rearrangements at nucleotide resolution by sequencing 141 breakpoints from cytogenetically interpreted translocations and inversions. We confirm that the recently described phenomenon of 'chromothripsis' (massive chromosomal shattering and reorganization) is not unique to cancer cells but also occurs in the germline, where it can resolve to a relatively balanced state with frequent inversions. We detected a high incidence of complex rearrangements (19.2%) and substantially less reliance on microhomology (31%) than previously observed in benign copy-number variants (CNVs). We compared these results to experimentally generated DNA breakage-repair by sequencing seven transgenic animals, revealing extensive rearrangement of the transgene and host genome with similar complexity to human germline alterations. Inversion was the most common rearrangement, suggesting that a combined mechanism involving template switching and non-homologous repair mediates the formation of balanced complex rearrangements that are viable, stably replicated and transmitted unaltered to subsequent generations. 相似文献
6.
Environmental light is the 'zeitgeber' (time-giver) of circadian behaviour. Constant darkness is considered a 'free-running' circadian state. Mammals encounter constant darkness during hibernation. Ablation of the master clock synchronizer, the suprachiasmatic nucleus, abolishes torpor, a hibernation-like state, implicating the circadian clock in this phenomenon. Here we report a mechanism by which constant darkness regulates the gene expression of fat catabolic enzymes in mice. Genes for murine procolipase (mClps) and pancreatic lipase-related protein 2 (mPlrp2) are activated in a circadian manner in peripheral organs during 12 h dark:12 h dark (DD) but not light-dark (LD) cycles. This mechanism is deregulated in circadian-deficient mPer1-/-/mPer2m/m mice. We identified circadian-regulated 5'-AMP, which is elevated in the blood of DD mice, as a key mediator of this response. Synthetic 5'-AMP induced torpor and mClps expression in LD animals. Torpor induced by metabolic stress was associated with elevated 5'-AMP levels in DD mice. Levels of glucose and non-esterified fatty acid in the blood are reversed in DD and LD mice. Induction of mClps expression by 5'-AMP in LD mice was reciprocally linked to blood glucose levels. Our findings uncover a circadian metabolic rhythm in mammals. 相似文献
7.
Kasahara M Naruse K Sasaki S Nakatani Y Qu W Ahsan B Yamada T Nagayasu Y Doi K Kasai Y Jindo T Kobayashi D Shimada A Toyoda A Kuroki Y Fujiyama A Sasaki T Shimizu A Asakawa S Shimizu N Hashimoto S Yang J Lee Y Matsushima K Sugano S Sakaizumi M Narita T Ohishi K Haga S Ohta F Nomoto H Nogata K Morishita T Endo T Shin-I T Takeda H Morishita S Kohara Y 《Nature》2007,447(7145):714-719
Teleosts comprise more than half of all vertebrate species and have adapted to a variety of marine and freshwater habitats. Their genome evolution and diversification are important subjects for the understanding of vertebrate evolution. Although draft genome sequences of two pufferfishes have been published, analysis of more fish genomes is desirable. Here we report a high-quality draft genome sequence of a small egg-laying freshwater teleost, medaka (Oryzias latipes). Medaka is native to East Asia and an excellent model system for a wide range of biology, including ecotoxicology, carcinogenesis, sex determination and developmental genetics. In the assembled medaka genome (700 megabases), which is less than half of the zebrafish genome, we predicted 20,141 genes, including approximately 2,900 new genes, using 5'-end serial analysis of gene expression tag information. We found single nucleotide polymorphisms (SNPs) at an average rate of 3.42% between the two inbred strains derived from two regional populations; this is the highest SNP rate seen in any vertebrate species. Analyses based on the dense SNP information show a strict genetic separation of 4 million years (Myr) between the two populations, and suggest that differential selective pressures acted on specific gene categories. Four-way comparisons with the human, pufferfish (Tetraodon), zebrafish and medaka genomes revealed that eight major interchromosomal rearrangements took place in a remarkably short period of approximately 50 Myr after the whole-genome duplication event in the teleost ancestor and afterwards, intriguingly, the medaka genome preserved its ancestral karyotype for more than 300 Myr. 相似文献
8.
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
9.
RNAi-mediated gene silencing in non-human primates 总被引:2,自引:0,他引:2
Zimmermann TS Lee AC Akinc A Bramlage B Bumcrot D Fedoruk MN Harborth J Heyes JA Jeffs LB John M Judge AD Lam K McClintock K Nechev LV Palmer LR Racie T Röhl I Seiffert S Shanmugam S Sood V Soutschek J Toudjarska I Wheat AJ Yaworski E Zedalis W Koteliansky V Manoharan M Vornlocher HP MacLachlan I 《Nature》2006,441(7089):111-114
The opportunity to harness the RNA interference (RNAi) pathway to silence disease-causing genes holds great promise for the development of therapeutics directed against targets that are otherwise not addressable with current medicines. Although there are numerous examples of in vivo silencing of target genes after local delivery of small interfering RNAs (siRNAs), there remain only a few reports of RNAi-mediated silencing in response to systemic delivery of siRNA, and there are no reports of systemic efficacy in non-rodent species. Here we show that siRNAs, when delivered systemically in a liposomal formulation, can silence the disease target apolipoprotein B (ApoB) in non-human primates. APOB-specific siRNAs were encapsulated in stable nucleic acid lipid particles (SNALP) and administered by intravenous injection to cynomolgus monkeys at doses of 1 or 2.5 mg kg(-1). A single siRNA injection resulted in dose-dependent silencing of APOB messenger RNA expression in the liver 48 h after administration, with maximal silencing of >90%. This silencing effect occurred as a result of APOB mRNA cleavage at precisely the site predicted for the RNAi mechanism. Significant reductions in ApoB protein, serum cholesterol and low-density lipoprotein levels were observed as early as 24 h after treatment and lasted for 11 days at the highest siRNA dose, thus demonstrating an immediate, potent and lasting biological effect of siRNA treatment. Our findings show clinically relevant RNAi-mediated gene silencing in non-human primates, supporting RNAi therapeutics as a potential new class of drugs. 相似文献
10.
Parton LE Ye CP Coppari R Enriori PJ Choi B Zhang CY Xu C Vianna CR Balthasar N Lee CE Elmquist JK Cowley MA Lowell BB 《Nature》2007,449(7159):228-232
A subset of neurons in the brain, known as 'glucose-excited' neurons, depolarize and increase their firing rate in response to increases in extracellular glucose. Similar to insulin secretion by pancreatic beta-cells, glucose excitation of neurons is driven by ATP-mediated closure of ATP-sensitive potassium (K(ATP)) channels. Although beta-cell-like glucose sensing in neurons is well established, its physiological relevance and contribution to disease states such as type 2 diabetes remain unknown. To address these issues, we disrupted glucose sensing in glucose-excited pro-opiomelanocortin (POMC) neurons via transgenic expression of a mutant Kir6.2 subunit (encoded by the Kcnj11 gene) that prevents ATP-mediated closure of K(ATP) channels. Here we show that this genetic manipulation impaired the whole-body response to a systemic glucose load, demonstrating a role for glucose sensing by POMC neurons in the overall physiological control of blood glucose. We also found that glucose sensing by POMC neurons became defective in obese mice on a high-fat diet, suggesting that loss of glucose sensing by neurons has a role in the development of type 2 diabetes. The mechanism for obesity-induced loss of glucose sensing in POMC neurons involves uncoupling protein 2 (UCP2), a mitochondrial protein that impairs glucose-stimulated ATP production. UCP2 negatively regulates glucose sensing in POMC neurons. We found that genetic deletion of Ucp2 prevents obesity-induced loss of glucose sensing, and that acute pharmacological inhibition of UCP2 reverses loss of glucose sensing. We conclude that obesity-induced, UCP2-mediated loss of glucose sensing in glucose-excited neurons might have a pathogenic role in the development of type 2 diabetes. 相似文献