全文获取类型
收费全文 | 1188篇 |
免费 | 2篇 |
国内免费 | 9篇 |
专业分类
系统科学 | 8篇 |
丛书文集 | 36篇 |
教育与普及 | 21篇 |
理论与方法论 | 4篇 |
现状及发展 | 75篇 |
研究方法 | 186篇 |
综合类 | 869篇 |
出版年
2024年 | 2篇 |
2023年 | 5篇 |
2022年 | 3篇 |
2020年 | 2篇 |
2018年 | 6篇 |
2017年 | 4篇 |
2016年 | 2篇 |
2015年 | 2篇 |
2014年 | 7篇 |
2013年 | 12篇 |
2012年 | 74篇 |
2011年 | 112篇 |
2010年 | 30篇 |
2009年 | 7篇 |
2008年 | 106篇 |
2007年 | 102篇 |
2006年 | 94篇 |
2005年 | 84篇 |
2004年 | 80篇 |
2003年 | 77篇 |
2002年 | 62篇 |
2001年 | 41篇 |
2000年 | 85篇 |
1999年 | 26篇 |
1998年 | 4篇 |
1997年 | 11篇 |
1995年 | 7篇 |
1994年 | 5篇 |
1993年 | 4篇 |
1992年 | 8篇 |
1991年 | 3篇 |
1990年 | 8篇 |
1989年 | 3篇 |
1986年 | 2篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1976年 | 1篇 |
1971年 | 4篇 |
1970年 | 13篇 |
1966年 | 2篇 |
1964年 | 1篇 |
1960年 | 1篇 |
1959年 | 13篇 |
1958年 | 22篇 |
1957年 | 16篇 |
1956年 | 6篇 |
1955年 | 8篇 |
1954年 | 9篇 |
1948年 | 11篇 |
1947年 | 1篇 |
排序方式: 共有1199条查询结果,搜索用时 546 毫秒
291.
Schwarz-Linek U Werner JM Pickford AR Gurusiddappa S Kim JH Pilka ES Briggs JA Gough TS Höök M Campbell ID Potts JR 《Nature》2003,423(6936):177-181
Staphylococcus aureus and Streptococcus pyogenes, two important human pathogens, target host fibronectin (Fn) in their adhesion to and invasion of host cells. Fibronectin-binding proteins (FnBPs), anchored in the bacterial cell wall, have multiple Fn-binding repeats in an unfolded region of the protein. The bacterium-binding site in the amino-terminal domain (1-5F1) of Fn contains five sequential Fn type 1 (F1) modules. Here we show the structure of a streptococcal (S. dysgalactiae) FnBP peptide (B3) in complex with the module pair 1F12F1. This identifies 1F1- and 2F1-binding motifs in B3 that form additional antiparallel beta-strands on sequential F1 modules-the first example of a tandem beta-zipper. Sequence analyses of larger regions of FnBPs from S. pyogenes and S. aureus reveal a repeating pattern of F1-binding motifs that match the pattern of F1 modules in 1-5F1 of Fn. In the process of Fn-mediated invasion of host cells, therefore, the bacterial proteins seem to exploit the modular structure of Fn by forming extended tandem beta-zippers. This work is a vital step forward in explaining the full mechanism of the integrin-dependent FnBP-mediated invasion of host cells. 相似文献
292.
孙见荆 《厦门大学学报(自然科学版)》1997,36(5):669-673
依据福建省“八五”重点软科学项目“福建省科技与经济,社会协调发展模型与系统分析”的研究,依据该省的实际情况,建立了以技术进步速度为核心的若干科技指标间的数量关系,为预测和控制区域技术进步对经济增长的贡献提供了一种思路。 相似文献
293.
294.
295.
实时监控中WEB发布技术的应用开发 总被引:3,自引:0,他引:3
文中介绍了工业企业的监控软件中实时数据和画面的WEB发布技术的应用开发,主要包括第三方关系数据库与实时数据库的连接和在WEB网页上的发布。通过一个实例建立起一个完整的实时监控WEB发布系统的过程。 相似文献
296.
针对传统电励磁双凸极发电机磁路长、本体质量大以及电机可靠性低的问题,提出了一种U形转子定子励磁发电机(UR-SEG)。该电机转子为分块U形结构以缩短电机磁路、减轻本体质量并改善了电机电动势波形。通过有限元仿真分析UR-SEG的电磁特性,其空载、负载电动势总谐波失真较传统电励磁双凸极发电机分别下降6.86%和7.28%,电机转子质量下降14.23%,改善了电机的发电质量。 相似文献
297.
Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in dominant intermediate Charcot-Marie-Tooth neuropathy 总被引:6,自引:0,他引:6
Jordanova A Irobi J Thomas FP Van Dijck P Meerschaert K Dewil M Dierick I Jacobs A De Vriendt E Guergueltcheva V Rao CV Tournev I Gondim FA D'Hooghe M Van Gerwen V Callaerts P Van Den Bosch L Timmermans JP Robberecht W Gettemans J Thevelein JM De Jonghe P Kremensky I Timmerman V 《Nature genetics》2006,38(2):197-202
Charcot-Marie-Tooth (CMT) neuropathies are common disorders of the peripheral nervous system caused by demyelination or axonal degeneration, or a combination of both features. We previously assigned the locus for autosomal dominant intermediate CMT neuropathy type C (DI-CMTC) to chromosome 1p34-p35. Here we identify two heterozygous missense mutations (G41R and E196K) and one de novo deletion (153-156delVKQV) in tyrosyl-tRNA synthetase (YARS) in three unrelated families affected with DI-CMTC. Biochemical experiments and genetic complementation in yeast show partial loss of aminoacylation activity of the mutant proteins, and mutations in YARS, or in its yeast ortholog TYS1, reduce yeast growth. YARS localizes to axonal termini in differentiating primary motor neuron and neuroblastoma cultures. This specific distribution is significantly reduced in cells expressing mutant YARS proteins. YARS is the second aminoacyl-tRNA synthetase found to be involved in CMT, thereby linking protein-synthesizing complexes with neurodegeneration. 相似文献
298.
A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep 总被引:38,自引:0,他引:38
Clop A Marcq F Takeda H Pirottin D Tordoir X Bibé B Bouix J Caiment F Elsen JM Eychenne F Larzul C Laville E Meish F Milenkovic D Tobin J Charlier C Georges M 《Nature genetics》2006,38(7):813-818
Texel sheep are renowned for their exceptional meatiness. To identify the genes underlying this economically important feature, we performed a whole-genome scan in a Romanov x Texel F2 population. We mapped a quantitative trait locus with a major effect on muscle mass to chromosome 2 and subsequently fine-mapped it to a chromosome interval encompassing the myostatin (GDF8) gene. We herein demonstrate that the GDF8 allele of Texel sheep is characterized by a G to A transition in the 3' UTR that creates a target site for mir1 and mir206, microRNAs (miRNAs) that are highly expressed in skeletal muscle. This causes translational inhibition of the myostatin gene and hence contributes to the muscular hypertrophy of Texel sheep. Analysis of SNP databases for humans and mice demonstrates that mutations creating or destroying putative miRNA target sites are abundant and might be important effectors of phenotypic variation. 相似文献
299.
Perlecan is a large multi-domain extracellular matrix proteoglycan that plays a crucial role in tissue development and organogenesis. In vertebrates, perlecan functions in a diverse range of developmental and biological processes, from the establishment of cartilage to the regulation of wound healing. How can a single molecule modulate such a wide variety of processes? We suggest that perlecan employs the same basic mechanism, based on interactions with growth factors, morphogens and matrix proteins, to regulate each of these processes and that the local extracellular environment determines the function of perlecan and consequently its downstream effects on the structure and function of the organ. We discuss this hypothesis in relation to its role in three major vertebrate developmental processes: angiogenesis, chondrogenesis and endochondral ossification. 相似文献
300.
Pozza A Perez-Victoria JM Sardo A Ahmed-Belkacem A Di Pietro A 《Cellular and molecular life sciences : CMLS》2006,63(16):1912-1922
Human ABCG2 was efficiently overexpressed in insect cell membranes, solubilized with 3-[(3-cholamidopropyl)dimethyl ammonio]-1-propanesulfonate,
and purified through N-terminal hexahistidine tag. Its functionality was assessed by high vanadate-sensitive ATPase activity, and nucleotide-binding
capacity. Interestingly, the R482T point mutation increased both maximal hydrolysis rate and affinity for MgATP, and lowered
sensitivity to vanadate inhibition. Direct nucleotide binding, as monitored by quenching of intrinsic fluorescence, indicated
a mutation-related preference for ATP over ADP. The R482T mutation only produced a limited change, if any, on the binding
of drug substrates, indicating that methotrexate, on the one hand, and rhodamine 123 or doxorubicin, on the other hand, bound
similarly to wild-type and mutant transporters whether or not they were subject to cellular transport. In addition, the characteristic
inhibitors GF120918 and 6-prenylchrysin, which alter mitoxantrone efflux much better for wild-type than mutant ABCG2, bound
similarly to purified ABCG2, while the highly-potent Ko143 bound in the nanomolar range also effective in inhibition of drug
transport. All results indicate that the role of the arginine-482 mutation on substrate drug transport and inhibitor efficiency
is not mediated by changes in drug binding.
Received 10 April 2006; received after revision 22 May 2006; accepted 12 June 2006
A. Pozza and J. M. Perez-Victoria contributed equally to this work 相似文献