全文获取类型
收费全文 | 540篇 |
免费 | 2篇 |
国内免费 | 3篇 |
专业分类
系统科学 | 7篇 |
教育与普及 | 1篇 |
理论与方法论 | 4篇 |
现状及发展 | 84篇 |
研究方法 | 78篇 |
综合类 | 338篇 |
自然研究 | 33篇 |
出版年
2018年 | 4篇 |
2017年 | 6篇 |
2015年 | 3篇 |
2013年 | 2篇 |
2012年 | 43篇 |
2011年 | 77篇 |
2010年 | 7篇 |
2009年 | 3篇 |
2008年 | 29篇 |
2007年 | 35篇 |
2006年 | 35篇 |
2005年 | 45篇 |
2004年 | 29篇 |
2003年 | 27篇 |
2002年 | 36篇 |
2001年 | 14篇 |
2000年 | 5篇 |
1999年 | 5篇 |
1995年 | 2篇 |
1993年 | 3篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1989年 | 5篇 |
1988年 | 8篇 |
1987年 | 2篇 |
1986年 | 7篇 |
1985年 | 6篇 |
1984年 | 8篇 |
1983年 | 6篇 |
1982年 | 6篇 |
1981年 | 4篇 |
1980年 | 1篇 |
1979年 | 3篇 |
1978年 | 1篇 |
1977年 | 3篇 |
1976年 | 7篇 |
1975年 | 4篇 |
1974年 | 4篇 |
1973年 | 5篇 |
1972年 | 2篇 |
1971年 | 8篇 |
1970年 | 9篇 |
1969年 | 1篇 |
1968年 | 4篇 |
1967年 | 5篇 |
1966年 | 6篇 |
1965年 | 5篇 |
1961年 | 2篇 |
1958年 | 1篇 |
1957年 | 3篇 |
排序方式: 共有545条查询结果,搜索用时 203 毫秒
521.
Structure of the intact transactivation domain of the human papillomavirus E2 protein 总被引:8,自引:0,他引:8
Antson AA Burns JE Moroz OV Scott DJ Sanders CM Bronstein IB Dodson GG Wilson KS Maitland NJ 《Nature》2000,403(6771):805-809
522.
A basic difficulty for the nervous system is integrating locally ambiguous sensory information to form accurate perceptions about the outside world. This local-to-global problem is also fundamental to motor control of the arm, because complex mechanical interactions between shoulder and elbow allow a particular amount of motion at one joint to arise from an infinite combination of shoulder and elbow torques. Here we show, in humans and rhesus monkeys, that a transcortical pathway through primary motor cortex (M1) resolves this ambiguity during fast feedback control. We demonstrate that single M1 neurons of behaving monkeys can integrate shoulder and elbow motion information into motor commands that appropriately counter the underlying torque within about 50 milliseconds of a mechanical perturbation. Moreover, we reveal a causal link between M1 processing and multi-joint integration in humans by showing that shoulder muscle responses occurring ~50 milliseconds after pure elbow displacement can be potentiated by transcranial magnetic stimulation. Taken together, our results show that transcortical processing through M1 permits feedback responses to express a level of sophistication that rivals voluntary control; this provides neurophysiological support for influential theories positing that voluntary movement is generated by the intelligent manipulation of sensory feedback. 相似文献
523.
Lee JM Lee YK Mamrosh JL Busby SA Griffin PR Pathak MC Ortlund EA Moore DD 《Nature》2011,474(7352):506-510
Nuclear hormone receptors regulate diverse metabolic pathways and the orphan nuclear receptor LRH-1 (also known as NR5A2) regulates bile acid biosynthesis. Structural studies have identified phospholipids as potential LRH-1 ligands, but their functional relevance is unclear. Here we show that an unusual phosphatidylcholine species with two saturated 12 carbon fatty acid acyl side chains (dilauroyl phosphatidylcholine (DLPC)) is an LRH-1 agonist ligand in vitro. DLPC treatment induces bile acid biosynthetic enzymes in mouse liver, increases bile acid levels, and lowers hepatic triglycerides and serum glucose. DLPC treatment also decreases hepatic steatosis and improves glucose homeostasis in two mouse models of insulin resistance. Both the antidiabetic and lipotropic effects are lost in liver-specific Lrh-1 knockouts. These findings identify an LRH-1 dependent phosphatidylcholine signalling pathway that regulates bile acid metabolism and glucose homeostasis. 相似文献
524.
Hansen SG Ford JC Lewis MS Ventura AB Hughes CM Coyne-Johnson L Whizin N Oswald K Shoemaker R Swanson T Legasse AW Chiuchiolo MJ Parks CL Axthelm MK Nelson JA Jarvis MA Piatak M Lifson JD Picker LJ 《Nature》2011,473(7348):523-527
The acquired immunodeficiency syndrome (AIDS)-causing lentiviruses human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) effectively evade host immunity and, once established, infections with these viruses are only rarely controlled by immunological mechanisms. However, the initial establishment of infection in the first few days after mucosal exposure, before viral dissemination and massive replication, may be more vulnerable to immune control. Here we report that SIV vaccines that include rhesus cytomegalovirus (RhCMV) vectors establish indefinitely persistent, high-frequency, SIV-specific effector memory T-cell (T(EM)) responses at potential sites of SIV replication in rhesus macaques and stringently control highly pathogenic SIV(MAC239) infection early after mucosal challenge. Thirteen of twenty-four rhesus macaques receiving either RhCMV vectors alone or RhCMV vectors followed by adenovirus 5 (Ad5) vectors (versus 0 of 9 DNA/Ad5-vaccinated rhesus macaques) manifested early complete control of SIV (undetectable plasma virus), and in twelve of these thirteen animals we observed long-term (≥1 year) protection. This was characterized by: occasional blips of plasma viraemia that ultimately waned; predominantly undetectable cell-associated viral load in blood and lymph node mononuclear cells; no depletion of effector-site CD4(+) memory T cells; no induction or boosting of SIV Env-specific antibodies; and induction and then loss of T-cell responses to an SIV protein (Vif) not included in the RhCMV vectors. Protection correlated with the magnitude of the peak SIV-specific CD8(+) T-cell responses in the vaccine phase, and occurred without anamnestic T-cell responses. Remarkably, long-term RhCMV vector-associated SIV control was insensitive to either CD8(+) or CD4(+) lymphocyte depletion and, at necropsy, cell-associated SIV was only occasionally measurable at the limit of detection with ultrasensitive assays, observations that indicate the possibility of eventual viral clearance. Thus, persistent vectors such as CMV and their associated T(EM) responses might significantly contribute to an efficacious HIV/AIDS vaccine. 相似文献
525.
Ehlmann BL Mustard JF Murchie SL Bibring JP Meunier A Fraeman AA Langevin Y 《Nature》2011,479(7371):53-60
Clay minerals, recently discovered to be widespread in Mars's Noachian terrains, indicate long-duration interaction between water and rock over 3.7 billion years ago. Analysis of how they formed should indicate what environmental conditions prevailed on early Mars. If clays formed near the surface by weathering, as is common on Earth, their presence would indicate past surface conditions warmer and wetter than at present. However, available data instead indicate substantial Martian clay formation by hydrothermal groundwater circulation and a Noachian rock record dominated by evidence of subsurface waters. Cold, arid conditions with only transient surface water may have characterized Mars's surface for over 4 billion years, since the early-Noachian period, and the longest-duration aqueous, potentially habitable environments may have been in the subsurface. 相似文献
526.
Structural basis of PIP2 activation of the classical inward rectifier K+ channel Kir2.2 总被引:1,自引:0,他引:1
The regulation of ion channel activity by specific lipid molecules is widely recognized as an integral component of electrical signalling in cells. In particular, phosphatidylinositol 4,5-bisphosphate (PIP(2)), a minor yet dynamic phospholipid component of cell membranes, is known to regulate many different ion channels. PIP(2) is the primary agonist for classical inward rectifier (Kir2) channels, through which this lipid can regulate a cell's resting membrane potential. However, the molecular mechanism by which PIP(2) exerts its action is unknown. Here we present the X-ray crystal structure of a Kir2.2 channel in complex with a short-chain (dioctanoyl) derivative of PIP(2). We found that PIP(2) binds at an interface between the transmembrane domain (TMD) and the cytoplasmic domain (CTD). The PIP(2)-binding site consists of a conserved non-specific phospholipid-binding region in the TMD and a specific phosphatidylinositol-binding region in the CTD. On PIP(2) binding, a flexible expansion linker contracts to a compact helical structure, the CTD translates 6 ? and becomes tethered to the TMD and the inner helix gate begins to open. In contrast, the small anionic lipid dioctanoyl glycerol pyrophosphatidic acid (PPA) also binds to the non-specific TMD region, but not to the specific phosphatidylinositol region, and thus fails to engage the CTD or open the channel. Our results show how PIP(2) can control the resting membrane potential through a specific ion-channel-receptor-ligand interaction that brings about a large conformational change, analogous to neurotransmitter activation of ion channels at synapses. 相似文献
527.
Abbot P Abe J Alcock J Alizon S Alpedrinha JA Andersson M Andre JB van Baalen M Balloux F Balshine S Barton N Beukeboom LW Biernaskie JM Bilde T Borgia G Breed M Brown S Bshary R Buckling A Burley NT Burton-Chellew MN Cant MA Chapuisat M Charnov EL Clutton-Brock T Cockburn A Cole BJ Colegrave N Cosmides L Couzin ID Coyne JA Creel S Crespi B Curry RL Dall SR Day T Dickinson JL Dugatkin LA El Mouden C Emlen ST Evans J Ferriere R Field J Foitzik S Foster K Foster WA Fox CW Gadau J Gandon S 《Nature》2011,471(7339):E1-4; author reply E9-10
Arising from M. A. Nowak, C. E. Tarnita & E. O. Wilson 466, 1057-1062 (2010); Nowak et al. reply. Nowak et al. argue that inclusive fitness theory has been of little value in explaining the natural world, and that it has led to negligible progress in explaining the evolution of eusociality. However, we believe that their arguments are based upon a misunderstanding of evolutionary theory and a misrepresentation of the empirical literature. We will focus our comments on three general issues. 相似文献
528.
529.
Hydrogen is an energy source for hydrothermal vent symbioses 总被引:1,自引:0,他引:1
Petersen JM Zielinski FU Pape T Seifert R Moraru C Amann R Hourdez S Girguis PR Wankel SD Barbe V Pelletier E Fink D Borowski C Bach W Dubilier N 《Nature》2011,476(7359):176-180
The discovery of deep-sea hydrothermal vents in 1977 revolutionized our understanding of the energy sources that fuel primary productivity on Earth. Hydrothermal vent ecosystems are dominated by animals that live in symbiosis with chemosynthetic bacteria. So far, only two energy sources have been shown to power chemosynthetic symbioses: reduced sulphur compounds and methane. Using metagenome sequencing, single-gene fluorescence in situ hybridization, immunohistochemistry, shipboard incubations and in situ mass spectrometry, we show here that the symbionts of the hydrothermal vent mussel Bathymodiolus from the Mid-Atlantic Ridge use hydrogen to power primary production. In addition, we show that the symbionts of Bathymodiolus mussels from Pacific vents have hupL, the key gene for hydrogen oxidation. Furthermore, the symbionts of other vent animals such as the tubeworm Riftia pachyptila and the shrimp Rimicaris exoculata also have hupL. We propose that the ability to use hydrogen as an energy source is widespread in hydrothermal vent symbioses, particularly at sites where hydrogen is abundant. 相似文献
530.
Near-surface wetland sediments as a source of arsenic release to ground water in Asia 总被引:4,自引:0,他引:4
Tens of millions of people in south and southeast Asia routinely consume ground water that has unsafe arsenic levels. Arsenic is naturally derived from eroded Himalayan sediments, and is believed to enter solution following reductive release from solid phases under anaerobic conditions. However, the processes governing aqueous concentrations and locations of arsenic release to pore water remain unresolved, limiting our ability to predict arsenic concentrations spatially (between wells) and temporally (future concentrations) and to assess the impact of human activities on the arsenic problem. This uncertainty is partly attributed to a poor understanding of groundwater flow paths altered by extensive irrigation pumping in the Ganges-Brahmaputra delta, where most research has focused. Here, using hydrologic and (bio)geochemical measurements, we show that on the minimally disturbed Mekong delta of Cambodia, arsenic is released from near-surface, river-derived sediments and transported, on a centennial timescale, through the underlying aquifer back to the river. Owing to similarities in geologic deposition, aquifer source rock and regional hydrologic gradients, our results represent a model for understanding pre-disturbance conditions for other major deltas in Asia. Furthermore, the observation of strong hydrologic influence on arsenic behaviour indicates that release and transport of arsenic are sensitive to continuing and impending anthropogenic disturbances. In particular, groundwater pumping for irrigation, changes in agricultural practices, sediment excavation, levee construction and upstream dam installations will alter the hydraulic regime and/or arsenic source material and, by extension, influence groundwater arsenic concentrations and the future of this health problem. 相似文献