全文获取类型
收费全文 | 304篇 |
免费 | 1篇 |
国内免费 | 1篇 |
专业分类
系统科学 | 5篇 |
教育与普及 | 1篇 |
理论与方法论 | 7篇 |
现状及发展 | 114篇 |
研究方法 | 48篇 |
综合类 | 130篇 |
自然研究 | 1篇 |
出版年
2020年 | 2篇 |
2018年 | 4篇 |
2017年 | 2篇 |
2016年 | 4篇 |
2015年 | 5篇 |
2014年 | 3篇 |
2013年 | 5篇 |
2012年 | 28篇 |
2011年 | 22篇 |
2010年 | 8篇 |
2008年 | 19篇 |
2007年 | 16篇 |
2006年 | 22篇 |
2005年 | 21篇 |
2004年 | 27篇 |
2003年 | 11篇 |
2002年 | 7篇 |
2001年 | 4篇 |
2000年 | 7篇 |
1999年 | 6篇 |
1998年 | 6篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1990年 | 2篇 |
1988年 | 3篇 |
1985年 | 5篇 |
1984年 | 2篇 |
1982年 | 1篇 |
1981年 | 3篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 3篇 |
1973年 | 1篇 |
1972年 | 3篇 |
1971年 | 10篇 |
1970年 | 4篇 |
1969年 | 3篇 |
1968年 | 1篇 |
1967年 | 4篇 |
1966年 | 2篇 |
1965年 | 1篇 |
1964年 | 1篇 |
1960年 | 2篇 |
1948年 | 2篇 |
1947年 | 2篇 |
1946年 | 1篇 |
1945年 | 1篇 |
排序方式: 共有306条查询结果,搜索用时 0 毫秒
131.
The subsolidus phase relations were determined experimentally in the system MgO-ZnO-SiO2 at 1.0 GPa and 1 200℃, by use of the high-pressure apparatus "piston-cylinder". The results showed characteristics of the phases assemblage different from that in similar ternary systems. It is impossible to form complete Mg2SiO4-Zn2SiO4 olivine and Mg2Si2O6-Zn2Si2O6 pyroxene solid solution. This is controlled by the properties of Zn2+ with an outer layer of electron (Ar)3d10, different from others transition metal ions, like Fe2+ , Ni2+ , Co2+ . 相似文献
132.
Kuijl C Savage ND Marsman M Tuin AW Janssen L Egan DA Ketema M van den Nieuwendijk R van den Eeden SJ Geluk A Poot A van der Marel G Beijersbergen RL Overkleeft H Ottenhoff TH Neefjes J 《Nature》2007,450(7170):725-730
With the emergence of multidrug resistant (MDR) bacteria, it is imperative to develop new intervention strategies. Current antibiotics typically target pathogen rather than host-specific biochemical pathways. Here we have developed kinase inhibitors that prevent intracellular growth of unrelated pathogens such as Salmonella typhimurium and Mycobacterium tuberculosis. An RNA interference screen of the human kinome using automated microscopy revealed several host kinases capable of inhibiting intracellular growth of S. typhimurium. The kinases identified clustered in one network around AKT1 (also known as PKB). Inhibitors of AKT1 prevent intracellular growth of various bacteria including MDR-M. tuberculosis. AKT1 is activated by the S. typhimurium effector SopB, which promotes intracellular survival by controlling actin dynamics through PAK4, and phagosome-lysosome fusion through the AS160 (also known as TBC1D4)-RAB14 pathway. AKT1 inhibitors counteract the bacterial manipulation of host signalling processes, thus controlling intracellular growth of bacteria. By using a reciprocal chemical genetics approach, we identified kinase inhibitors with antibiotic properties and their host targets, and we determined host signalling networks that are activated by intracellular bacteria for survival. 相似文献
133.
Fic proteins that are defined by the ubiquitous FIC (filamentation induced by cyclic AMP) domain are known to catalyse adenylylation (also called AMPylation); that is, the transfer of AMP onto a target protein. In mammalian cells, adenylylation of small GTPases through Fic proteins injected by pathogenic bacteria can cause collapse of the actin cytoskeleton and cell death. It is unknown how this potentially deleterious adenylylation activity is regulated in the widespread Fic proteins that are found in all domains of life and that are thought to have critical roles in intrinsic signalling processes. Here we show that FIC-domain-mediated adenylylation is controlled by a conserved mechanism of ATP-binding-site obstruction that involves an inhibitory α-helix (α(inh)) with a conserved (S/T)XXXE(G/N) motif, and that in this mechanism the invariable glutamate competes with ATP γ-phosphate binding. Consistent with this, FIC-domain-mediated growth arrest of bacteria by the VbhT toxin of Bartonella schoenbuchensis is intermolecularly repressed by the VbhA antitoxin through tight binding of its α(inh) to the FIC domain of VbhT, as shown by structure and function analysis. Furthermore, structural comparisons with other bacterial Fic proteins, such as Fic of Neisseria meningitidis and of Shewanella oneidensis, show that α(inh) frequently constitutes an amino-terminal or carboxy-terminal extension to the FIC domain, respectively, partially obstructing the ATP binding site in an intramolecular manner. After mutation of the inhibitory motif in various Fic proteins, including the human homologue FICD (also known as HYPE), adenylylation activity is considerably boosted, consistent with the anticipated relief of inhibition. Structural homology modelling of all annotated Fic proteins indicates that inhibition by α(inh) is universal and conserved through evolution, as the inhibitory motif is present in ~90% of all putatively adenylylation-active FIC domains, including examples from all domains of life and from viruses. Future studies should reveal how intrinsic or extrinsic factors modulate adenylylation activity by weakening the interaction of α(inh) with the FIC active site. 相似文献
134.
The dynamics of a single impurity in an environment is a fundamental problem in many-body physics. In the solid state, a well known case is an impurity coupled to a bosonic bath (such as lattice vibrations); the impurity and its accompanying lattice distortion form a new entity, a polaron. This quasiparticle plays an important role in the spectral function of high-transition-temperature superconductors, as well as in colossal magnetoresistance in manganites. For impurities in a fermionic bath, studies have considered heavy or immobile impurities which exhibit Anderson's orthogonality catastrophe and the Kondo effect. More recently, mobile impurities have moved into the focus of research, and they have been found to form new quasiparticles known as Fermi polarons. The Fermi polaron problem constitutes the extreme, but conceptually simple, limit of two important quantum many-body problems: the crossover between a molecular Bose-Einstein condensate and a superfluid with BCS (Bardeen-Cooper-Schrieffer) pairing with spin-imbalance for attractive interactions, and Stoner's itinerant ferromagnetism for repulsive interactions. It has been proposed that such quantum phases (and other elusive exotic states) might become realizable in Fermi gases confined to two dimensions. Their stability and observability are intimately related to the theoretically debated properties of the Fermi polaron in a two-dimensional Fermi gas. Here we create and investigate Fermi polarons in a two-dimensional, spin-imbalanced Fermi gas, measuring their spectral function using momentum-resolved photoemission spectroscopy. For attractive interactions, we find evidence for a disputed pairing transition between polarons and tightly bound dimers, which provides insight into the elementary pairing mechanism of imbalanced, strongly coupled two-dimensional Fermi gases. Additionally, for repulsive interactions, we study novel quasiparticles--repulsive polarons--the lifetime of which determines the possibility of stabilizing repulsively interacting Fermi systems. 相似文献
135.
A 'snowball Earth' climate triggered by continental break-up through changes in runoff 总被引:1,自引:0,他引:1
Geological and palaeomagnetic studies indicate that ice sheets may have reached the Equator at the end of the Proterozoic eon, 800 to 550 million years ago, leading to the suggestion of a fully ice-covered 'snowball Earth'. Climate model simulations indicate that such a snowball state for the Earth depends on anomalously low atmospheric carbon dioxide concentrations, in addition to the Sun being 6 per cent fainter than it is today. However, the mechanisms producing such low carbon dioxide concentrations remain controversial. Here we assess the effect of the palaeogeographic changes preceding the Sturtian glacial period, 750 million years ago, on the long-term evolution of atmospheric carbon dioxide levels using the coupled climate-geochemical model GEOCLIM. In our simulation, the continental break-up of Rodinia leads to an increase in runoff and hence consumption of carbon dioxide through continental weathering that decreases atmospheric carbon dioxide concentrations by 1,320 p.p.m. This indicates that tectonic changes could have triggered a progressive transition from a 'greenhouse' to an 'icehouse' climate during the Neoproterozoic era. When we combine these results with the concomitant weathering effect of the voluminous basaltic traps erupted throughout the break-up of Rodinia, our simulation results in a snowball glaciation. 相似文献
136.
Reactive aldehydes are common carcinogens. They are also by-products of several metabolic pathways and, without enzymatic catabolism, may accumulate and cause DNA damage. Ethanol, which is metabolised to acetaldehyde, is both carcinogenic and teratogenic in humans. Here we find that the Fanconi anaemia DNA repair pathway counteracts acetaldehyde-induced genotoxicity in mice. Our results show that the acetaldehyde-catabolising enzyme Aldh2 is essential for the development of Fancd2(-/-) embryos. Nevertheless, acetaldehyde-catabolism-competent mothers (Aldh2(+/-)) can support the development of double-mutant (Aldh2(-/-)Fancd2(-/-)) mice. However, these embryos are unusually sensitive to ethanol exposure in utero, and ethanol consumption by postnatal double-deficient mice rapidly precipitates bone marrow failure. Lastly, Aldh2(-/-)Fancd2(-/-) mice spontaneously develop acute leukaemia. Acetaldehyde-mediated DNA damage may critically contribute to the genesis of fetal alcohol syndrome in fetuses, as well as to abnormal development, haematopoietic failure and cancer predisposition in Fanconi anaemia patients. 相似文献
137.
Genome duplication in the teleost fish Tetraodon nigroviridis reveals the early vertebrate proto-karyotype 总被引:2,自引:0,他引:2
Jaillon O Aury JM Brunet F Petit JL Stange-Thomann N Mauceli E Bouneau L Fischer C Ozouf-Costaz C Bernot A Nicaud S Jaffe D Fisher S Lutfalla G Dossat C Segurens B Dasilva C Salanoubat M Levy M Boudet N Castellano S Anthouard V Jubin C Castelli V Katinka M Vacherie B Biémont C Skalli Z Cattolico L Poulain J De Berardinis V Cruaud C Duprat S Brottier P Coutanceau JP Gouzy J Parra G Lardier G Chapple C McKernan KJ McEwan P Bosak S Kellis M Volff JN Guigó R Zody MC Mesirov J Lindblad-Toh K 《Nature》2004,431(7011):946-957
Tetraodon nigroviridis is a freshwater puffer fish with the smallest known vertebrate genome. Here, we report a draft genome sequence with long-range linkage and substantial anchoring to the 21 Tetraodon chromosomes. Genome analysis provides a greatly improved fish gene catalogue, including identifying key genes previously thought to be absent in fish. Comparison with other vertebrates and a urochordate indicates that fish proteins have diverged markedly faster than their mammalian homologues. Comparison with the human genome suggests approximately 900 previously unannotated human genes. Analysis of the Tetraodon and human genomes shows that whole-genome duplication occurred in the teleost fish lineage, subsequent to its divergence from mammals. The analysis also makes it possible to infer the basic structure of the ancestral bony vertebrate genome, which was composed of 12 chromosomes, and to reconstruct much of the evolutionary history of ancient and recent chromosome rearrangements leading to the modern human karyotype. 相似文献
138.
Gonzalez MR Bischofberger M Pernot L van der Goot FG Frêche B 《Cellular and molecular life sciences : CMLS》2008,65(3):493-507
Pore-forming toxins (PFTs) are the most common class of bacterial protein toxins and constitute important bacterial virulence
factors. The mode of action of PFT is starting to be better understood. In contrast, little is known about the cellular response
to this threat. Recent studies reveal that cells do not just swell and lyse, but are able to sense and react to pore formation,
mount a defense, even repair the damaged membrane and thus survive. These responses involve a variety of signal-transduction
pathways and sophisticated cellular mechanisms such as the pathway regulating lipid metabolism. In this review we discuss
the different classes of bacterial PFTs and their modes of action, and provide examples of how the different bacteria use
PFTs. Finally, we address the more recent field dealing with the eukaryotic cell response to PFT-induced damage.
Received 19 September 2007; received after revision 18 October 2007; accepted 23 October 2007 相似文献
139.
D. S. Nelson S. Kossaŕd Prudence E. Cox 《Cellular and molecular life sciences : CMLS》1967,23(6):490-491
Résumé Des souris immunisés avec des globules rouges de mouton dans l'adjuvant de Freund produisent deux types de facteurs cytophiles pour macrophages. L'un s'attache aux macrophages trypsinisées et se trouve parmi les immunoglobulines. L'autre ne s'attache pas aux macrophages trypsinisées et se rencontre dans une fraction de sérum contenant de l'albumine et de la globuline-1.
Supported by grants from the Australian Research Grants Committee, the National Health and Medical Research Council of Australia and the Postgraduate Medical Foundation, University of Sydney. 相似文献
Supported by grants from the Australian Research Grants Committee, the National Health and Medical Research Council of Australia and the Postgraduate Medical Foundation, University of Sydney. 相似文献
140.