全文获取类型
收费全文 | 439篇 |
免费 | 3篇 |
国内免费 | 9篇 |
专业分类
系统科学 | 6篇 |
教育与普及 | 1篇 |
理论与方法论 | 8篇 |
现状及发展 | 85篇 |
研究方法 | 62篇 |
综合类 | 285篇 |
自然研究 | 4篇 |
出版年
2021年 | 7篇 |
2019年 | 2篇 |
2018年 | 11篇 |
2017年 | 7篇 |
2016年 | 10篇 |
2015年 | 7篇 |
2014年 | 4篇 |
2013年 | 8篇 |
2012年 | 40篇 |
2011年 | 59篇 |
2010年 | 18篇 |
2009年 | 3篇 |
2008年 | 34篇 |
2007年 | 40篇 |
2006年 | 28篇 |
2005年 | 35篇 |
2004年 | 21篇 |
2003年 | 21篇 |
2002年 | 21篇 |
2001年 | 7篇 |
2000年 | 5篇 |
1999年 | 4篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1991年 | 2篇 |
1990年 | 4篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1983年 | 3篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1973年 | 1篇 |
1972年 | 4篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1969年 | 2篇 |
1967年 | 1篇 |
1966年 | 3篇 |
1964年 | 2篇 |
1962年 | 1篇 |
1957年 | 1篇 |
1945年 | 1篇 |
排序方式: 共有451条查询结果,搜索用时 31 毫秒
1.
2.
Earman (2018) has recently argued that the Principal Principle, a principle of rationality connecting objective chance and credence, is a theorem of quantum probability theory. This paper critiques Earman's argument, while also offering a positive proposal for how to understand the status of the Principal Principle in quantum probability theory. 相似文献
3.
Samuel A. Alexander 《Journal of Classification》2016,33(1):103-117
Nested clusters arise independently in graph partitioning and in the study of contours. We take a step toward unifying these two instances of nested clusters. We show that the graph theoretical tight clusters introduced by Dress, Steel, Moulton and Wu in 2010 are a special case of nested clusters associated to contours. 相似文献
4.
5.
6.
BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module 总被引:1,自引:0,他引:1
Park D Tosello-Trampont AC Elliott MR Lu M Haney LB Ma Z Klibanov AL Mandell JW Ravichandran KS 《Nature》2007,450(7168):430-434
Engulfment and subsequent degradation of apoptotic cells is an essential step that occurs throughout life in all multicellular organisms. ELMO/Dock180/Rac proteins are a conserved signalling module for promoting the internalization of apoptotic cell corpses; ELMO and Dock180 function together as a guanine nucleotide exchange factor (GEF) for the small GTPase Rac, and thereby regulate the phagocyte actin cytoskeleton during engulfment. However, the receptor(s) upstream of the ELMO/Dock180/Rac module are still unknown. Here we identify brain-specific angiogenesis inhibitor 1 (BAI1) as a receptor upstream of ELMO and as a receptor that can bind phosphatidylserine on apoptotic cells. BAI1 is a seven-transmembrane protein belonging to the adhesion-type G-protein-coupled receptor family, with an extended extracellular region and no known ligands. We show that BAI1 functions as an engulfment receptor in both the recognition and subsequent internalization of apoptotic cells. Through multiple lines of investigation, we identify phosphatidylserine, a key 'eat-me' signal exposed on apoptotic cells, as a ligand for BAI1. The thrombospondin type 1 repeats within the extracellular region of BAI1 mediate direct binding to phosphatidylserine. As with intracellular signalling, BAI1 forms a trimeric complex with ELMO and Dock180, and functional studies suggest that BAI1 cooperates with ELMO/Dock180/Rac to promote maximal engulfment of apoptotic cells. Last, decreased BAI1 expression or interference with BAI1 function inhibits the engulfment of apoptotic targets ex vivo and in vivo. Thus, BAI1 is a phosphatidylserine recognition receptor that can directly recruit a Rac-GEF complex to mediate the uptake of apoptotic cells. 相似文献
7.
Stark A Lin MF Kheradpour P Pedersen JS Parts L Carlson JW Crosby MA Rasmussen MD Roy S Deoras AN Ruby JG Brennecke J;Harvard FlyBase curators;Berkeley Drosophila Genome Project Hodges E Hinrichs AS Caspi A Paten B Park SW Han MV Maeder ML Polansky BJ Robson BE Aerts S van Helden J Hassan B Gilbert DG Eastman DA Rice M Weir M Hahn MW Park Y Dewey CN Pachter L Kent WJ Haussler D Lai EC Bartel DP Hannon GJ Kaufman TC Eisen MB Clark AG Smith D Celniker SE Gelbart WM Kellis M 《Nature》2007,450(7167):219-232
8.
Most local anaesthetics used clinically are relatively hydrophobic molecules that gain access to their blocking site on the sodium channel by diffusing into or through the cell membrane. These anaesthetics block sodium channels and thereby the excitability of all neurons, not just sensory neurons. We tested the possibility of selectively blocking the excitability of primary sensory nociceptor (pain-sensing) neurons by introducing the charged, membrane-impermeant lidocaine derivative QX-314 through the pore of the noxious-heat-sensitive TRPV1 channel. Here we show that charged sodium-channel blockers can be targeted into nociceptors by the application of TRPV1 agonists to produce a pain-specific local anaesthesia. QX-314 applied externally had no effect on the activity of sodium channels in small sensory neurons when applied alone, but when applied in the presence of the TRPV1 agonist capsaicin, QX-314 blocked sodium channels and inhibited excitability. Inhibition by co-applied QX-314 and capsaicin was restricted to neurons expressing TRPV1. Injection of QX-314 together with capsaicin into rat hindpaws produced a long-lasting (more than 2 h) increase in mechanical and thermal nociceptive thresholds. Long-lasting decreases in pain sensitivity were also seen with regional injection of QX-314 and capsaicin near the sciatic nerve; however, in contrast to the effect of lidocaine, the application of QX-314 and capsaicin together was not accompanied by motor or tactile deficits. 相似文献
9.
Zhang F Wang LP Brauner M Liewald JF Kay K Watzke N Wood PG Bamberg E Nagel G Gottschalk A Deisseroth K 《Nature》2007,446(7136):633-639
Our understanding of the cellular implementation of systems-level neural processes like action, thought and emotion has been limited by the availability of tools to interrogate specific classes of neural cells within intact, living brain tissue. Here we identify and develop an archaeal light-driven chloride pump (NpHR) from Natronomonas pharaonis for temporally precise optical inhibition of neural activity. NpHR allows either knockout of single action potentials, or sustained blockade of spiking. NpHR is compatible with ChR2, the previous optical excitation technology we have described, in that the two opposing probes operate at similar light powers but with well-separated action spectra. NpHR, like ChR2, functions in mammals without exogenous cofactors, and the two probes can be integrated with calcium imaging in mammalian brain tissue for bidirectional optical modulation and readout of neural activity. Likewise, NpHR and ChR2 can be targeted together to Caenorhabditis elegans muscle and cholinergic motor neurons to control locomotion bidirectionally. NpHR and ChR2 form a complete system for multimodal, high-speed, genetically targeted, all-optical interrogation of living neural circuits. 相似文献
10.
Mackereth CD Madl T Bonnal S Simon B Zanier K Gasch A Rybin V Valcárcel J Sattler M 《Nature》2011,475(7356):408-411
Many cellular functions involve multi-domain proteins, which are composed of structurally independent modules connected by flexible linkers. Although it is often well understood how a given domain recognizes a cognate oligonucleotide or peptide motif, the dynamic interaction of multiple domains in the recognition of these ligands remains to be characterized. Here we have studied the molecular mechanisms of the recognition of the 3'-splice-site-associated polypyrimidine tract RNA by the large subunit of the human U2 snRNP auxiliary factor (U2AF65) as a key early step in pre-mRNA splicing. We show that the tandem RNA recognition motif domains of U2AF65 adopt two remarkably distinct domain arrangements in the absence or presence of a strong (that is, high affinity) polypyrimidine tract. Recognition of sequence variations in the polypyrimidine tract RNA involves a population shift between these closed and open conformations. The equilibrium between the two conformations functions as a molecular rheostat that quantitatively correlates the natural variations in polypyrimidine tract nucleotide composition, length and functional strength to the efficiency to recruit U2 snRNP to the intron during spliceosome assembly. Mutations that shift the conformational equilibrium without directly affecting RNA binding modulate splicing activity accordingly. Similar mechanisms of cooperative multi-domain conformational selection may operate more generally in the recognition of degenerate nucleotide or amino acid motifs by multi-domain proteins. 相似文献