首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   30722篇
  免费   70篇
  国内免费   85篇
系统科学   319篇
丛书文集   661篇
教育与普及   64篇
理论与方法论   117篇
现状及发展   14607篇
研究方法   1150篇
综合类   13648篇
自然研究   311篇
  2012年   348篇
  2011年   711篇
  2010年   154篇
  2009年   152篇
  2008年   430篇
  2007年   515篇
  2006年   498篇
  2005年   509篇
  2004年   579篇
  2003年   520篇
  2002年   459篇
  2001年   897篇
  2000年   905篇
  1999年   560篇
  1992年   527篇
  1991年   420篇
  1990年   485篇
  1989年   462篇
  1988年   409篇
  1987年   446篇
  1986年   481篇
  1985年   596篇
  1984年   426篇
  1983年   387篇
  1982年   361篇
  1981年   409篇
  1980年   432篇
  1979年   1030篇
  1978年   840篇
  1977年   823篇
  1976年   625篇
  1975年   702篇
  1974年   1044篇
  1973年   827篇
  1972年   807篇
  1971年   985篇
  1970年   1232篇
  1969年   1032篇
  1968年   960篇
  1967年   977篇
  1966年   816篇
  1965年   647篇
  1964年   196篇
  1959年   369篇
  1958年   575篇
  1957年   411篇
  1956年   347篇
  1955年   341篇
  1954年   334篇
  1948年   206篇
排序方式: 共有10000条查询结果,搜索用时 444 毫秒
411.
Structure of a nanobody-stabilized active state of the β(2) adrenoceptor   总被引:1,自引:0,他引:1  
G protein coupled receptors (GPCRs) exhibit a spectrum of functional behaviours in response to natural and synthetic ligands. Recent crystal structures provide insights into inactive states of several GPCRs. Efforts to obtain an agonist-bound active-state GPCR structure have proven difficult due to the inherent instability of this state in the absence of a G protein. We generated a camelid antibody fragment (nanobody) to the human β(2) adrenergic receptor (β(2)AR) that exhibits G protein-like behaviour, and obtained an agonist-bound, active-state crystal structure of the receptor-nanobody complex. Comparison with the inactive β(2)AR structure reveals subtle changes in the binding pocket; however, these small changes are associated with an 11?? outward movement of the cytoplasmic end of transmembrane segment 6, and rearrangements of transmembrane segments 5 and 7 that are remarkably similar to those observed in opsin, an active form of rhodopsin. This structure provides insights into the process of agonist binding and activation.  相似文献   
412.
413.
Adipose tissue mass is determined by the storage and removal of triglycerides in adipocytes. Little is known, however, about adipose lipid turnover in humans in health and pathology. To study this in vivo, here we determined lipid age by measuring (14)C derived from above ground nuclear bomb tests in adipocyte lipids. We report that during the average ten-year lifespan of human adipocytes, triglycerides are renewed six times. Lipid age is independent of adipocyte size, is very stable across a wide range of adult ages and does not differ between genders. Adipocyte lipid turnover, however, is strongly related to conditions with disturbed lipid metabolism. In obesity, triglyceride removal rate (lipolysis followed by oxidation) is decreased and the amount of triglycerides stored each year is increased. In contrast, both lipid removal and storage rates are decreased in non-obese patients diagnosed with the most common hereditary form of dyslipidaemia, familial combined hyperlipidaemia. Lipid removal rate is positively correlated with the capacity of adipocytes to break down triglycerides, as assessed through lipolysis, and is inversely related to insulin resistance. Our data support a mechanism in which adipocyte lipid storage and removal have different roles in health and pathology. High storage but low triglyceride removal promotes fat tissue accumulation and obesity. Reduction of both triglyceride storage and removal decreases lipid shunting through adipose tissue and thus promotes dyslipidaemia. We identify adipocyte lipid turnover as a novel target for prevention and treatment of metabolic disease.  相似文献   
414.
415.
Quantum decoherence is a central concept in physics. Applications such as quantum information processing depend on understanding it; there are even fundamental theories proposed that go beyond quantum mechanics, in which the breakdown of quantum theory would appear as an 'intrinsic' decoherence, mimicking the more familiar environmental decoherence processes. Such applications cannot be optimized, and such theories cannot be tested, until we have a firm handle on ordinary environmental decoherence processes. Here we show that the theory for insulating electronic spin systems can make accurate and testable predictions for environmental decoherence in molecular-based quantum magnets. Experiments on molecular magnets have successfully demonstrated quantum-coherent phenomena but the decoherence processes that ultimately limit such behaviour were not well constrained. For molecular magnets, theory predicts three principal contributions to environmental decoherence: from phonons, from nuclear spins and from intermolecular dipolar interactions. We use high magnetic fields on single crystals of Fe(8) molecular magnets (in which the Fe ions are surrounded by organic ligands) to suppress dipolar and nuclear-spin decoherence. In these high-field experiments, we find that the decoherence time varies strongly as a function of temperature and magnetic field. The theoretical predictions are fully verified experimentally, and there are no other visible decoherence sources. In these high fields, we obtain a maximum decoherence quality-factor of 1.49?×?10(6); our investigation suggests that the environmental decoherence time can be extended up to about 500 microseconds, with a decoherence quality factor of ~6?×?10(7), by optimizing the temperature, magnetic field and nuclear isotopic concentrations.  相似文献   
416.
Crystal structure of the β2 adrenergic receptor-Gs protein complex   总被引:1,自引:0,他引:1  
G protein-coupled receptors (GPCRs) are responsible for the majority of cellular responses to hormones and neurotransmitters as well as the senses of sight, olfaction and taste. The paradigm of GPCR signalling is the activation of a heterotrimeric GTP binding protein (G protein) by an agonist-occupied receptor. The β(2) adrenergic receptor (β(2)AR) activation of Gs, the stimulatory G protein for adenylyl cyclase, has long been a model system for GPCR signalling. Here we present the crystal structure of the active state ternary complex composed of agonist-occupied monomeric β(2)AR and nucleotide-free Gs heterotrimer. The principal interactions between the β(2)AR and Gs involve the amino- and carboxy-terminal α-helices of Gs, with conformational changes propagating to the nucleotide-binding pocket. The largest conformational changes in the β(2)AR include a 14 ? outward movement at the cytoplasmic end of transmembrane segment 6 (TM6) and an α-helical extension of the cytoplasmic end of TM5. The most surprising observation is a major displacement of the α-helical domain of Gαs relative to the Ras-like GTPase domain. This crystal structure represents the first high-resolution view of transmembrane signalling by a GPCR.  相似文献   
417.
418.
Microtubules have pivotal roles in fundamental cellular processes and are targets of antitubulin chemotherapeutics. Microtubule-targeted agents such as Taxol and vincristine are prescribed widely for various malignancies, including ovarian and breast adenocarcinomas, non-small-cell lung cancer, leukaemias and lymphomas. These agents arrest cells in mitosis and subsequently induce cell death through poorly defined mechanisms. The strategies that resistant tumour cells use to evade death induced by antitubulin agents are also unclear. Here we show that the pro-survival protein MCL1 (ref. 3) is a crucial regulator of apoptosis triggered by antitubulin chemotherapeutics. During mitotic arrest, MCL1 protein levels decline markedly, through a post-translational mechanism, potentiating cell death. Phosphorylation of MCL1 directs its interaction with the tumour-suppressor protein FBW7, which is the substrate-binding component of a ubiquitin ligase complex. The polyubiquitylation of MCL1 then targets it for proteasomal degradation. The degradation of MCL1 was blocked in patient-derived tumour cells that lacked FBW7 or had loss-of-function mutations in FBW7, conferring resistance to antitubulin agents and promoting chemotherapeutic-induced polyploidy. Additionally, primary tumour samples were enriched for FBW7 inactivation and elevated MCL1 levels, underscoring the prominent roles of these proteins in oncogenesis. Our findings suggest that profiling the FBW7 and MCL1 status of tumours, in terms of protein levels, messenger RNA levels and genetic status, could be useful to predict the response of patients to antitubulin chemotherapeutics.  相似文献   
419.
Reconstructed changes in Arctic sea ice over the past 1,450 years   总被引:1,自引:0,他引:1  
Arctic sea ice extent is now more than two million square kilometres less than it was in the late twentieth century, with important consequences for the climate, the ocean and traditional lifestyles in the Arctic. Although observations show a more or less continuous decline for the past four or five decades, there are few long-term records with which to assess natural sea ice variability. Until now, the question of whether or not current trends are potentially anomalous has therefore remained unanswerable. Here we use a network of high-resolution terrestrial proxies from the circum-Arctic region to reconstruct past extents of summer sea ice, and show that-although extensive uncertainties remain, especially before the sixteenth century-both the duration and magnitude of the current decline in sea ice seem to be unprecedented for the past 1,450 years. Enhanced advection of warm Atlantic water to the Arctic seems to be the main factor driving the decline of sea ice extent on multidecadal timescales, and may result from nonlinear feedbacks between sea ice and the Atlantic meridional overturning circulation. These results reinforce the assertion that sea ice is an active component of Arctic climate variability and that the recent decrease in summer Arctic sea ice is consistent with anthropogenically forced warming.  相似文献   
420.
Steric effects in chemistry are a consequence of the space required to accommodate the atoms and groups within a molecule, and are often thought to be dominated by repulsive forces arising from overlapping electron densities (Pauli repulsion). An appreciation of attractive interactions such as van der Waals forces (which include London dispersion forces) is necessary to understand chemical bonding and reactivity fully. This is evident from, for example, the strongly debated origin of the higher stability of branched alkanes relative to linear alkanes and the possibility of constructing hydrocarbons with extraordinarily long C-C single bonds through steric crowding. Although empirical bond distance/bond strength relationships have been established for C-C bonds (longer C-C bonds have smaller bond dissociation energies), these have no present theoretical basis. Nevertheless, these empirical considerations are fundamental to structural and energetic evaluations in chemistry, as summarized by Pauling as early as 1960 and confirmed more recently. Here we report the preparation of hydrocarbons with extremely long C-C bonds (up to 1.704??), the longest such bonds observed so far in alkanes. The prepared compounds are unexpectedly stable--noticeable decomposition occurs only above 200?°C. We prepared the alkanes by coupling nanometre-sized, diamond-like, highly rigid structures known as diamondoids. The extraordinary stability of the coupling products is due to overall attractive dispersion interactions between the intramolecular H???H contact surfaces, as is evident from density functional theory computations with and without inclusion of dispersion corrections.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号