全文获取类型
收费全文 | 7926篇 |
免费 | 87篇 |
国内免费 | 114篇 |
专业分类
系统科学 | 134篇 |
丛书文集 | 393篇 |
教育与普及 | 346篇 |
理论与方法论 | 24篇 |
现状及发展 | 674篇 |
研究方法 | 1046篇 |
综合类 | 5505篇 |
自然研究 | 5篇 |
出版年
2021年 | 13篇 |
2018年 | 13篇 |
2017年 | 24篇 |
2016年 | 23篇 |
2015年 | 18篇 |
2014年 | 34篇 |
2013年 | 40篇 |
2012年 | 493篇 |
2011年 | 616篇 |
2010年 | 190篇 |
2009年 | 106篇 |
2008年 | 617篇 |
2007年 | 589篇 |
2006年 | 663篇 |
2005年 | 687篇 |
2004年 | 502篇 |
2003年 | 467篇 |
2002年 | 384篇 |
2001年 | 333篇 |
2000年 | 506篇 |
1999年 | 187篇 |
1998年 | 51篇 |
1997年 | 23篇 |
1996年 | 26篇 |
1994年 | 27篇 |
1993年 | 32篇 |
1992年 | 21篇 |
1991年 | 32篇 |
1990年 | 25篇 |
1989年 | 37篇 |
1988年 | 25篇 |
1987年 | 25篇 |
1986年 | 37篇 |
1985年 | 36篇 |
1984年 | 33篇 |
1983年 | 31篇 |
1982年 | 37篇 |
1981年 | 30篇 |
1980年 | 13篇 |
1979年 | 21篇 |
1971年 | 16篇 |
1970年 | 29篇 |
1966年 | 11篇 |
1959年 | 116篇 |
1958年 | 216篇 |
1957年 | 153篇 |
1956年 | 122篇 |
1955年 | 129篇 |
1954年 | 146篇 |
1948年 | 34篇 |
排序方式: 共有8127条查询结果,搜索用时 0 毫秒
191.
Prud'homme B Minervino C Hocine M Cande JD Aouane A Dufour HD Kassner VA Gompel N 《Nature》2011,473(7345):83-86
Body plans, which characterize the anatomical organization of animal groups of high taxonomic rank, often evolve by the reduction or loss of appendages (limbs in vertebrates and legs and wings in insects, for example). In contrast, the addition of new features is extremely rare and is thought to be heavily constrained, although the nature of the constraints remains elusive. Here we show that the treehopper (Membracidae) 'helmet' is actually an appendage, a wing serial homologue on the first thoracic segment. This innovation in the insect body plan is an unprecedented situation in 250 Myr of insect evolution. We provide evidence suggesting that the helmet arose by escaping the ancestral repression of wing formation imparted by a member of the Hox gene family, which sculpts the number and pattern of appendages along the body axis. Moreover, we propose that the exceptional morphological diversification of the helmet was possible because, in contrast to the wings, it escaped the stringent functional requirements imposed by flight. This example illustrates how complex morphological structures can arise by the expression of ancestral developmental potentials and fuel the morphological diversification of an evolutionary lineage. 相似文献
192.
Zuber J Shi J Wang E Rappaport AR Herrmann H Sison EA Magoon D Qi J Blatt K Wunderlich M Taylor MJ Johns C Chicas A Mulloy JC Kogan SC Brown P Valent P Bradner JE Lowe SW Vakoc CR 《Nature》2011,478(7370):524-528
Epigenetic pathways can regulate gene expression by controlling and interpreting chromatin modifications. Cancer cells are characterized by altered epigenetic landscapes, and commonly exploit the chromatin regulatory machinery to enforce oncogenic gene expression programs. Although chromatin alterations are, in principle, reversible and often amenable to drug intervention, the promise of targeting such pathways therapeutically has been limited by an incomplete understanding of cancer-specific dependencies on epigenetic regulators. Here we describe a non-biased approach to probe epigenetic vulnerabilities in acute myeloid leukaemia (AML), an aggressive haematopoietic malignancy that is often associated with aberrant chromatin states. By screening a custom library of small hairpin RNAs (shRNAs) targeting known chromatin regulators in a genetically defined AML mouse model, we identify the protein bromodomain-containing 4 (Brd4) as being critically required for disease maintenance. Suppression of Brd4 using shRNAs or the small-molecule inhibitor JQ1 led to robust antileukaemic effects in vitro and in vivo, accompanied by terminal myeloid differentiation and elimination of leukaemia stem cells. Similar sensitivities were observed in a variety of human AML cell lines and primary patient samples, revealing that JQ1 has broad activity in diverse AML subtypes. The effects of Brd4 suppression are, at least in part, due to its role in sustaining Myc expression to promote aberrant self-renewal, which implicates JQ1 as a pharmacological means to suppress MYC in cancer. Our results establish small-molecule inhibition of Brd4 as a promising therapeutic strategy in AML and, potentially, other cancers, and highlight the utility of RNA interference (RNAi) screening for revealing epigenetic vulnerabilities that can be exploited for direct pharmacological intervention. 相似文献
193.
Rothberg JM Hinz W Rearick TM Schultz J Mileski W Davey M Leamon JH Johnson K Milgrew MJ Edwards M Hoon J Simons JF Marran D Myers JW Davidson JF Branting A Nobile JR Puc BP Light D Clark TA Huber M Branciforte JT Stoner IB Cawley SE Lyons M Fu Y Homer N Sedova M Miao X Reed B Sabina J Feierstein E Schorn M Alanjary M Dimalanta E Dressman D Kasinskas R Sokolsky T Fidanza JA Namsaraev E McKernan KJ Williams A Roth GT Bustillo J 《Nature》2011,475(7356):348-352
The seminal importance of DNA sequencing to the life sciences, biotechnology and medicine has driven the search for more scalable and lower-cost solutions. Here we describe a DNA sequencing technology in which scalable, low-cost semiconductor manufacturing techniques are used to make an integrated circuit able to directly perform non-optical DNA sequencing of genomes. Sequence data are obtained by directly sensing the ions produced by template-directed DNA polymerase synthesis using all-natural nucleotides on this massively parallel semiconductor-sensing device or ion chip. The ion chip contains ion-sensitive, field-effect transistor-based sensors in perfect register with 1.2 million wells, which provide confinement and allow parallel, simultaneous detection of independent sequencing reactions. Use of the most widely used technology for constructing integrated circuits, the complementary metal-oxide semiconductor (CMOS) process, allows for low-cost, large-scale production and scaling of the device to higher densities and larger array sizes. We show the performance of the system by sequencing three bacterial genomes, its robustness and scalability by producing ion chips with up to 10 times as many sensors and sequencing a human genome. 相似文献
194.
195.
196.
Radu I Vahaplar K Stamm C Kachel T Pontius N Dürr HA Ostler TA Barker J Evans RF Chantrell RW Tsukamoto A Itoh A Kirilyuk A Rasing T Kimel AV 《Nature》2011,472(7342):205-208
Ferromagnetic or antiferromagnetic spin ordering is governed by the exchange interaction, the strongest force in magnetism. Understanding spin dynamics in magnetic materials is an issue of crucial importance for progress in information processing and recording technology. Usually the dynamics are studied by observing the collective response of exchange-coupled spins, that is, spin resonances, after an external perturbation by a pulse of magnetic field, current or light. The periods of the corresponding resonances range from one nanosecond for ferromagnets down to one picosecond for antiferromagnets. However, virtually nothing is known about the behaviour of spins in a magnetic material after being excited on a timescale faster than that corresponding to the exchange interaction (10-100?fs), that is, in a non-adiabatic way. Here we use the element-specific technique X-ray magnetic circular dichroism to study spin reversal in GdFeCo that is optically excited on a timescale pertinent to the characteristic time of the exchange interaction between Gd and Fe spins. We unexpectedly find that the ultrafast spin reversal in this material, where spins are coupled antiferromagnetically, occurs by way of a transient ferromagnetic-like state. Following the optical excitation, the net magnetizations of the Gd and Fe sublattices rapidly collapse, switch their direction and rebuild their net magnetic moments at substantially different timescales; the net magnetic moment of the Gd sublattice is found to reverse within 1.5 picoseconds, which is substantially slower than the Fe reversal time of 300 femtoseconds. Consequently, a transient state characterized by a temporary parallel alignment of the net Gd and Fe moments emerges, despite their ground-state antiferromagnetic coupling. These surprising observations, supported by atomistic simulations, provide a concept for the possibility of manipulating magnetic order on the timescale of the exchange interaction. 相似文献
197.
Electrons moving in two dimensions under the influence of strong magnetic fields effectively lose their kinetic energy and display exotic behaviour dominated by Coulomb forces. When the ratio of electrons to magnetic flux quanta in the system (ν) is near 5/2, the electrons are predicted to condense into a correlated phase with fractionally charged quasiparticles and a ground-state degeneracy that grows exponentially as these quasiparticles are introduced. The only way for electrons to transform between the many ground states would be to braid the fractional excitations around each other. This property has been proposed as the basis of a fault-tolerant quantum computer. Here we present observations of localized quasiparticles at ν = 5/2, confined to puddles by disorder. Using a local electrometer to compare how quasiparticles at ν = 5/2 and ν = 7/3 charge these puddles, we were able to extract the ratio of local charges for these states. Averaged over several disorder configurations and samples, we found the ratio to be 4/3, suggesting that the local charges are = e/3 and = e/4, where e is the charge of an electron. This is in agreement with theoretical predictions for a paired state at ν = 5/2. Confirming the existence of localized e/4 quasiparticles shows that proposed interferometry experiments to test statistics and computational ability of the state at ν = 5/2 would be possible. 相似文献
198.
199.
Cell-type-specific replication initiation programs set fragility of the FRA3B fragile site 总被引:7,自引:0,他引:7
Letessier A Millot GA Koundrioukoff S Lachagès AM Vogt N Hansen RS Malfoy B Brison O Debatisse M 《Nature》2011,470(7332):120-123
Common fragile sites have long been identified by cytogeneticists as chromosomal regions prone to breakage upon replication stress. They are increasingly recognized to be preferential targets for oncogene-induced DNA damage in pre-neoplastic lesions and hotspots for chromosomal rearrangements in various cancers. Common fragile site instability was attributed to the fact that they contain sequences prone to form secondary structures that may impair replication fork movement, possibly leading to fork collapse resulting in DNA breaks. Here we show, in contrast to this view, that the fragility of FRA3B--the most active common fragile site in human lymphocytes--does not rely on fork slowing or stalling but on a paucity of initiation events. Indeed, in lymphoblastoid cells, but not in fibroblasts, initiation events are excluded from a FRA3B core extending approximately 700 kilobases, which forces forks coming from flanking regions to cover long distances in order to complete replication. We also show that origins of the flanking regions fire in mid-S phase, leaving the site incompletely replicated upon fork slowing. Notably, FRA3B instability is specific to cells showing this particular initiation pattern. The fact that both origin setting and replication timing are highly plastic in mammalian cells explains the tissue specificity of common fragile site instability we observed. Thus, we propose that common fragile sites correspond to the latest initiation-poor regions to complete replication in a given cell type. For historical reasons, common fragile sites have been essentially mapped in lymphocytes. Therefore, common fragile site contribution to chromosomal rearrangements in tumours should be reassessed after mapping fragile sites in the cell type from which each tumour originates. 相似文献
200.