全文获取类型
收费全文 | 485篇 |
免费 | 3篇 |
国内免费 | 3篇 |
专业分类
系统科学 | 10篇 |
教育与普及 | 1篇 |
理论与方法论 | 5篇 |
现状及发展 | 194篇 |
研究方法 | 92篇 |
综合类 | 179篇 |
自然研究 | 10篇 |
出版年
2018年 | 14篇 |
2017年 | 9篇 |
2016年 | 13篇 |
2015年 | 11篇 |
2014年 | 9篇 |
2013年 | 14篇 |
2012年 | 45篇 |
2011年 | 54篇 |
2010年 | 22篇 |
2009年 | 9篇 |
2008年 | 33篇 |
2007年 | 23篇 |
2006年 | 33篇 |
2005年 | 25篇 |
2004年 | 30篇 |
2003年 | 22篇 |
2002年 | 23篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1997年 | 2篇 |
1995年 | 2篇 |
1991年 | 1篇 |
1987年 | 1篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 6篇 |
1980年 | 6篇 |
1979年 | 3篇 |
1978年 | 2篇 |
1977年 | 8篇 |
1976年 | 4篇 |
1975年 | 5篇 |
1974年 | 2篇 |
1973年 | 8篇 |
1972年 | 6篇 |
1971年 | 6篇 |
1970年 | 4篇 |
1969年 | 2篇 |
1968年 | 2篇 |
1966年 | 3篇 |
1965年 | 2篇 |
1964年 | 3篇 |
1962年 | 1篇 |
1960年 | 1篇 |
1959年 | 1篇 |
1957年 | 1篇 |
1956年 | 1篇 |
1955年 | 5篇 |
1954年 | 1篇 |
1947年 | 1篇 |
排序方式: 共有491条查询结果,搜索用时 31 毫秒
1.
Maria Luisa Dalla Chiara 《Foundations of Science》2002,7(1-2):1-9
In recent times, a particular attention has been devoted to thesignificance of Quantum Theory for other disciplines. The articlescollected in this issue discuss some interesting cases,characterized by an interaction between Quantum Theory andother fields. Some basic notrons of the mathematical formalismof the theory are here summarized. 相似文献
2.
This paper stresses the restrictive nature of the standard unit root/cointegration assumptions and examines a more general type of time heterogeneity, which might characterize a number of economic variables, and which results in parameter time dependence and misleading statistical inference. We show that in such cases ‘operational’ models cannot be obtained, and the estimation of time‐varying parameter models becomes necessary. For instance, economic processes subject to endemic change can only be adequately modelled in a state space form. This is a very important point, because unstable models will break down when used for forecasting purposes. We also discuss a new test for the null of cointegration developed by Quintos and Phillips (1993), which is based on parameter constancy in cointegrating regressions. Finally, we point out that, if it is possible to condition on a subset of superexogenous variables, parameter instability can be handled by estimating a restricted system. Copyright © 2002 John Wiley & Sons, Ltd. 相似文献
3.
P. J. Müller P. Masner Maria Kälin W. S. Bowers 《Cellular and molecular life sciences : CMLS》1979,35(5):704-705
Summary Corpora allata fromOncopeltus fasciatus incubated in vitro in medium containing 10–5.35 M (1 g/ml) of precocene II lose their ability to secrete juvenile hormone when reimplanted into last instar larvae.Acknowledgments. We thank Mr K. Dorn, Mrs L. Dolezal, Mrs V. Nötzli-Graf, Mr K.H. Trautmann and Mr A. Schuler for technical help, Dr W. Vogel and Dr A. Dübendorfer for valuable discussions. 相似文献
4.
Silvia Bassani Alessandra Folci Jonathan Zapata Maria Passafaro 《Cellular and molecular life sciences : CMLS》2013,70(23):4411-4430
Glutamate ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPARs) mediate most fast excitatory synaptic transmission in the central nervous system. The content and composition of AMPARs in postsynaptic membranes (which determine synaptic strength) are dependent on the regulated trafficking of AMPAR subunits in and out of the membranes. AMPAR trafficking is a key mechanism that drives nascent synapse development, and is the main determinant of both Hebbian and homeostatic plasticity in mature synapses. Hebbian plasticity seems to be the biological substrate of at least some forms of learning and memory; while homeostatic plasticity (also known as synaptic scaling) keeps neuronal circuits stable by maintaining changes within a physiological range. In this review, we examine recent findings that provide further understanding of the role of AMPAR trafficking in synapse maturation, Hebbian plasticity, and homeostatic plasticity. 相似文献
5.
Gandin V Miluzio A Barbieri AM Beugnet A Kiyokawa H Marchisio PC Biffo S 《Nature》2008,455(7213):684-688
Cell growth and proliferation require coordinated ribosomal biogenesis and translation. Eukaryotic initiation factors (eIFs) control translation at the rate-limiting step of initiation. So far, only two eIFs connect extracellular stimuli to global translation rates: eIF4E acts in the eIF4F complex and regulates binding of capped messenger RNA to 40S subunits, downstream of growth factors, and eIF2 controls loading of the ternary complex on the 40S subunit and is inhibited on stress stimuli. No eIFs have been found to link extracellular stimuli to the activity of the large 60S ribosomal subunit. eIF6 binds 60S ribosomes precluding ribosome joining in vitro. However, studies in yeasts showed that eIF6 is required for ribosome biogenesis rather than translation. Here we show that mammalian eIF6 is required for efficient initiation of translation, in vivo. eIF6 null embryos are lethal at preimplantation. Heterozygous mice have 50% reduction of eIF6 levels in all tissues, and show reduced mass of hepatic and adipose tissues due to a lower number of cells and to impaired G1/S cell cycle progression. eIF6(+/-) cells retain sufficient nucleolar eIF6 and normal ribosome biogenesis. The liver of eIF6(+/-) mice displays an increase of 80S in polysomal profiles, indicating a defect in initiation of translation. Consistently, isolated hepatocytes have impaired insulin-stimulated translation. Heterozygous mouse embryonic fibroblasts recapitulate the organism phenotype and have normal ribosome biogenesis, reduced insulin-stimulated translation, and delayed G1/S phase progression. Furthermore, eIF6(+/-) cells are resistant to oncogene-induced transformation. Thus, eIF6 is the first eIF associated with the large 60S subunit that regulates translation in response to extracellular signals. 相似文献
6.
Kittler R Putz G Pelletier L Poser I Heninger AK Drechsel D Fischer S Konstantinova I Habermann B Grabner H Yaspo ML Himmelbauer H Korn B Neugebauer K Pisabarro MT Buchholz F 《Nature》2004,432(7020):1036-1040
RNA interference (RNAi) is an evolutionarily conserved defence mechanism whereby genes are specifically silenced through degradation of messenger RNAs; this process is mediated by homologous double-stranded (ds)RNA molecules. In invertebrates, long dsRNAs have been used for genome-wide screens and have provided insights into gene functions. Because long dsRNA triggers a nonspecific interferon response in many vertebrates, short interfering (si)RNA or short hairpin (sh)RNAs must be used for these organisms to ensure specific gene silencing. Here we report the generation of a genome-scale library of endoribonuclease-prepared short interfering (esi)RNAs from a sequence-verified complementary DNA collection representing 15,497 human genes. We used 5,305 esiRNAs from this library to screen for genes required for cell division in HeLa cells. Using a primary high-throughput cell viability screen followed by a secondary high content videomicroscopy assay, we identified 37 genes required for cell division. These include several splicing factors for which knockdown generates mitotic spindle defects. In addition, a putative nuclear-export terminator was found to speed up cell proliferation and mitotic progression after knockdown. Thus, our study uncovers new aspects of cell division and establishes esiRNA as a versatile approach for genomic RNAi screens in mammalian cells. 相似文献
7.
Genome sequencing in microfabricated high-density picolitre reactors 总被引:21,自引:0,他引:21
Margulies M Egholm M Altman WE Attiya S Bader JS Bemben LA Berka J Braverman MS Chen YJ Chen Z Dewell SB Du L Fierro JM Gomes XV Godwin BC He W Helgesen S Ho CH Ho CH Irzyk GP Jando SC Alenquer ML Jarvie TP Jirage KB Kim JB Knight JR Lanza JR Leamon JH Lefkowitz SM Lei M Li J Lohman KL Lu H Makhijani VB McDade KE McKenna MP Myers EW Nickerson E Nobile JR Plant R Puc BP Ronan MT Roth GT Sarkis GJ Simons JF Simpson JW Srinivasan M Tartaro KR Tomasz A Vogt KA Volkmer GA Wang SH Wang Y Weiner MP 《Nature》2005,437(7057):376-380
The proliferation of large-scale DNA-sequencing projects in recent years has driven a search for alternative methods to reduce time and cost. Here we describe a scalable, highly parallel sequencing system with raw throughput significantly greater than that of state-of-the-art capillary electrophoresis instruments. The apparatus uses a novel fibre-optic slide of individual wells and is able to sequence 25 million bases, at 99% or better accuracy, in one four-hour run. To achieve an approximately 100-fold increase in throughput over current Sanger sequencing technology, we have developed an emulsion method for DNA amplification and an instrument for sequencing by synthesis using a pyrosequencing protocol optimized for solid support and picolitre-scale volumes. Here we show the utility, throughput, accuracy and robustness of this system by shotgun sequencing and de novo assembly of the Mycoplasma genitalium genome with 96% coverage at 99.96% accuracy in one run of the machine. 相似文献
8.
Maria C. Shina Annette Müller-Taubenberger Can Ünal Michael Schleicher Michael Steinert Ludwig Eichinger Rolf Müller Rosemarie Blau-Wasser Gernot Glöckner Angelika A. Noegel 《Cellular and molecular life sciences : CMLS》2011,68(2):303-313
Dictyostelium discoideum harbors a short (CRN12) and a long coronin (CRN7) composed of one and two beta-propellers, respectively. They are primarily
present in the cell cortex and cells lacking CRN12 (corA
−) or CRN7 (corB
−) have defects in actin driven processes. We compared the characteristics of a mutant cell line (corA
−
/corB
−) lacking CRN12 and CRN7 with the single mutants focusing on cytokinesis, phagocytosis, chemotaxis and development. Cytokinesis,
uptake of small particles, and developmental defects were not enhanced in the corA
−
/corB
− strain as compared to the single mutants, whereas motility and phagocytosis of yeast particles were more severely impaired.
It appears that although both proteins affect the same processes they do not act in a redundant manner. Rather, they often
act antagonistically, which is in accordance with their proposed roles in the actin cytoskeleton where CRN12 acts in actin
disassembly whereas CRN7 stabilizes actin filaments and protects them from disassembly. 相似文献
9.
In higher vertebrates, sulfatases belong to a conserved family of enzymes that are involved in the regulation of cell metabolism
and in developmental cell signaling. They cleave the sulfate from sulfate esters contained in hormones, proteins, and complex
macromolecules. A highly conserved cysteine in their active site is post-translationally converted into formylglycine by the
formylglycine-generating enzyme encoded by SUMF1 (sulfatase modifying factor 1). This post-translational modification activates all sulfatases. Sulfatases are extensively
glycosylated proteins and some of them follow trafficking pathways through cells, being secreted and taken up by distant cells.
Many proteoglycans, glycoproteins, and glycolipids contain sulfated carbohydrates, which are sulfatase substrates. Indeed,
sulfatases operate as decoding factors for a large amount of biological information contained in the structures of the sulfated
sugar chains that are covalently linked to proteins and lipids. Modifications to these sulfate groups have pivotal roles in
modulating specific signaling pathways and cell metabolism in mammals. 相似文献
10.
Robert W. Buckheit III Maria Salgado Karen O. Martins Joel N. Blankson 《Cellular and molecular life sciences : CMLS》2013,70(6):1009-1019
The mechanisms by which a small percentage of HIV-1 infected individuals known as elite suppressors or controllers are able to control viral replication are not fully understood. Early cases of viremic control were attributed to infection with defective virus, but subsequent work has demonstrated that infection with a defective virus is not the exclusive cause of control. Replication-competent virus has been isolated from patients who control viral replication, and studies have demonstrated that evolution occurs in plasma virus but not in virus isolates from the latent reservoir. Additionally, transmission pair studies have demonstrated that patients infected with similar viruses can have dramatically different outcomes of infection. An increased understanding of the viral factors associated with control is important to understand the interplay between viral replication and host control, and has implications for the design of an effective therapeutic vaccine that can lead to a functional cure of HIV-1 infection. 相似文献