全文获取类型
收费全文 | 18656篇 |
免费 | 97篇 |
国内免费 | 238篇 |
专业分类
系统科学 | 398篇 |
丛书文集 | 382篇 |
教育与普及 | 75篇 |
理论与方法论 | 66篇 |
现状及发展 | 6310篇 |
研究方法 | 889篇 |
综合类 | 10329篇 |
自然研究 | 542篇 |
出版年
2014年 | 143篇 |
2013年 | 295篇 |
2012年 | 541篇 |
2011年 | 1086篇 |
2010年 | 381篇 |
2009年 | 352篇 |
2008年 | 593篇 |
2007年 | 677篇 |
2006年 | 661篇 |
2005年 | 598篇 |
2004年 | 449篇 |
2003年 | 349篇 |
2002年 | 365篇 |
2001年 | 509篇 |
2000年 | 561篇 |
1999年 | 411篇 |
1992年 | 290篇 |
1991年 | 253篇 |
1990年 | 250篇 |
1989年 | 229篇 |
1988年 | 209篇 |
1987年 | 227篇 |
1986年 | 203篇 |
1985年 | 245篇 |
1984年 | 235篇 |
1983年 | 159篇 |
1982年 | 172篇 |
1981年 | 157篇 |
1980年 | 199篇 |
1979年 | 445篇 |
1978年 | 341篇 |
1977年 | 367篇 |
1976年 | 264篇 |
1975年 | 322篇 |
1974年 | 447篇 |
1973年 | 379篇 |
1972年 | 360篇 |
1971年 | 421篇 |
1970年 | 484篇 |
1969年 | 425篇 |
1968年 | 407篇 |
1967年 | 443篇 |
1966年 | 384篇 |
1965年 | 301篇 |
1959年 | 155篇 |
1958年 | 231篇 |
1957年 | 179篇 |
1956年 | 138篇 |
1955年 | 154篇 |
1954年 | 132篇 |
排序方式: 共有10000条查询结果,搜索用时 13 毫秒
351.
Supermassive black holes are now thought to lie at the heart of every giant galaxy with a spheroidal component, including our own Milky Way. The birth and growth of the first 'seed' black holes in the earlier Universe, however, is observationally unconstrained and we are only beginning to piece together a scenario for their subsequent evolution. Here we report that the nearby dwarf starburst galaxy Henize?2-10 (refs 5 and 6) contains a compact radio source at the dynamical centre of the galaxy that is spatially coincident with a hard X-ray source. From these observations, we conclude that Henize?2-10 harbours an actively accreting central black hole with a mass of approximately one million solar masses. This nearby dwarf galaxy, simultaneously hosting a massive black hole and an extreme burst of star formation, is analogous in many ways to galaxies in the infant Universe during the early stages of black-hole growth and galaxy mass assembly. Our results confirm that nearby star-forming dwarf galaxies can indeed form massive black holes, and that by implication so can their primordial counterparts. Moreover, the lack of a substantial spheroidal component in Henize?2-10 indicates that supermassive black-hole growth may precede the build-up of galaxy spheroids. 相似文献
352.
Arner P Bernard S Salehpour M Possnert G Liebl J Steier P Buchholz BA Eriksson M Arner E Hauner H Skurk T Rydén M Frayn KN Spalding KL 《Nature》2011,478(7367):110-113
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
353.
Kaneko H Dridi S Tarallo V Gelfand BD Fowler BJ Cho WG Kleinman ME Ponicsan SL Hauswirth WW Chiodo VA Karikó K Yoo JW Lee DK Hadziahmetovic M Song Y Misra S Chaudhuri G Buaas FW Braun RE Hinton DR Zhang Q Grossniklaus HE Provis JM Madigan MC Milam AH Justice NL Albuquerque RJ Blandford AD Bogdanovich S Hirano Y Witta J Fuchs E Littman DR Ambati BK Rudin CM Chong MM Provost P Kugel JF Goodrich JA Dunaief JL Baffi JZ Ambati J 《Nature》2011,471(7338):325-330
354.
Rasmussen SG DeVree BT Zou Y Kruse AC Chung KY Kobilka TS Thian FS Chae PS Pardon E Calinski D Mathiesen JM Shah ST Lyons JA Caffrey M Gellman SH Steyaert J Skiniotis G Weis WI Sunahara RK Kobilka BK 《Nature》2011,477(7366):549-555
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
355.
356.
357.
Wertz IE Kusam S Lam C Okamoto T Sandoval W Anderson DJ Helgason E Ernst JA Eby M Liu J Belmont LD Kaminker JS O'Rourke KM Pujara K Kohli PB Johnson AR Chiu ML Lill JR Jackson PK Fairbrother WJ Seshagiri S Ludlam MJ Leong KG Dueber EC Maecker H Huang DC Dixit VM 《Nature》2011,471(7336):110-114
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
358.
Learning causes a change in how information is processed by neuronal circuits. Whereas synaptic plasticity, an important cellular mechanism, has been studied in great detail, we know much less about how learning is implemented at the level of neuronal circuits and, in particular, how interactions between distinct types of neurons within local networks contribute to the process of learning. Here we show that acquisition of associative fear memories depends on the recruitment of a disinhibitory microcircuit in the mouse auditory cortex. Fear-conditioning-associated disinhibition in auditory cortex is driven by foot-shock-mediated cholinergic activation of layer 1 interneurons, in turn generating inhibition of layer 2/3 parvalbumin-positive interneurons. Importantly, pharmacological or optogenetic block of pyramidal neuron disinhibition abolishes fear learning. Together, these data demonstrate that stimulus convergence in the auditory cortex is necessary for associative fear learning to complex tones, define the circuit elements mediating this convergence and suggest that layer-1-mediated disinhibition is an important mechanism underlying learning and information processing in neocortical circuits. 相似文献
359.
Jones JT Hasell T Wu X Bacsa J Jelfs KE Schmidtmann M Chong SY Adams DJ Trewin A Schiffman F Cora F Slater B Steiner A Day GM Cooper AI 《Nature》2011,474(7351):367-371
Nanoporous molecular frameworks are important in applications such as separation, storage and catalysis. Empirical rules exist for their assembly but it is still challenging to place and segregate functionality in three-dimensional porous solids in a predictable way. Indeed, recent studies of mixed crystalline frameworks suggest a preference for the statistical distribution of functionalities throughout the pores rather than, for example, the functional group localization found in the reactive sites of enzymes. This is a potential limitation for 'one-pot' chemical syntheses of porous frameworks from simple starting materials. An alternative strategy is to prepare porous solids from synthetically preorganized molecular pores. In principle, functional organic pore modules could be covalently prefabricated and then assembled to produce materials with specific properties. However, this vision of mix-and-match assembly is far from being realized, not least because of the challenge in reliably predicting three-dimensional structures for molecular crystals, which lack the strong directional bonding found in networks. Here we show that highly porous crystalline solids can be produced by mixing different organic cage modules that self-assemble by means of chiral recognition. The structures of the resulting materials can be predicted computationally, allowing in silico materials design strategies. The constituent pore modules are synthesized in high yields on gram scales in a one-step reaction. Assembly of the porous co-crystals is as simple as combining the modules in solution and removing the solvent. In some cases, the chiral recognition between modules can be exploited to produce porous organic nanoparticles. We show that the method is valid for four different cage modules and can in principle be generalized in a computationally predictable manner based on a lock-and-key assembly between modules. 相似文献
360.
Ramsden S Richardson FM Josse G Thomas MS Ellis C Shakeshaft C Seghier ML Price CJ 《Nature》2011,479(7371):113-116
Intelligence quotient (IQ) is a standardized measure of human intellectual capacity that takes into account a wide range of cognitive skills. IQ is generally considered to be stable across the lifespan, with scores at one time point used to predict educational achievement and employment prospects in later years. Neuroimaging allows us to test whether unexpected longitudinal fluctuations in measured IQ are related to brain development. Here we show that verbal and non-verbal IQ can rise or fall in the teenage years, with these changes in performance validated by their close correlation with changes in local brain structure. A combination of structural and functional imaging showed that verbal IQ changed with grey matter in a region that was activated by speech, whereas non-verbal IQ changed with grey matter in a region that was activated by finger movements. By using longitudinal assessments of the same individuals, we obviated the many sources of variation in brain structure that confound cross-sectional studies. This allowed us to dissociate neural markers for the two types of IQ and to show that general verbal and non-verbal abilities are closely linked to the sensorimotor skills involved in learning. More generally, our results emphasize the possibility that an individual's intellectual capacity relative to their peers can decrease or increase in the teenage years. This would be encouraging to those whose intellectual potential may improve, and would be a warning that early achievers may not maintain their potential. 相似文献