全文获取类型
收费全文 | 78篇 |
免费 | 0篇 |
专业分类
现状及发展 | 37篇 |
研究方法 | 12篇 |
综合类 | 29篇 |
出版年
2022年 | 1篇 |
2018年 | 1篇 |
2017年 | 1篇 |
2016年 | 4篇 |
2015年 | 3篇 |
2013年 | 2篇 |
2012年 | 4篇 |
2011年 | 12篇 |
2010年 | 4篇 |
2009年 | 1篇 |
2008年 | 4篇 |
2007年 | 4篇 |
2006年 | 4篇 |
2005年 | 5篇 |
2004年 | 3篇 |
2003年 | 5篇 |
2002年 | 2篇 |
1991年 | 1篇 |
1989年 | 1篇 |
1982年 | 2篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1973年 | 2篇 |
1970年 | 1篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1966年 | 1篇 |
1965年 | 1篇 |
1964年 | 1篇 |
1962年 | 2篇 |
1959年 | 1篇 |
排序方式: 共有78条查询结果,搜索用时 234 毫秒
1.
Watson DM Bohac CJ Hull C Forrest WJ Furlan E Najita J Calvet N d'Alessio P Hartmann L Sargent B Green JD Kim KH Houck JR 《Nature》2007,448(7157):1026-1028
Class 0 protostars, the youngest type of young stellar objects, show many signs of rapid development from their initial, spheroidal configurations, and therefore are studied intensively for details of the formation of protoplanetary disks within protostellar envelopes. At millimetre wavelengths, kinematic signatures of collapse have been observed in several such protostars, through observations of molecular lines that probe their outer envelopes. It has been suggested that one or more components of the proto-multiple system NGC 1333-IRAS 4 (refs 1, 2) may display signs of an embedded region that is warmer and denser than the bulk of the envelope. Here we report observations that reveal details of the core on Solar System dimensions. We detect in NGC 1333-IRAS 4B a rich emission spectrum of H2O, at wavelengths 20-37 microm, which indicates an origin in extremely dense, warm gas. We can model the emission as infall from a protostellar envelope onto the surface of a deeply embedded, dense disk, and therefore see the development of a protoplanetary disk. This is the only example of mid-infrared water emission from a sample of 30 class 0 objects, perhaps arising from a favourable orientation; alternatively, this may be an early and short-lived stage in the evolution of a protoplanetary disk. 相似文献
2.
Carette JE Raaben M Wong AC Herbert AS Obernosterer G Mulherkar N Kuehne AI Kranzusch PJ Griffin AM Ruthel G Dal Cin P Dye JM Whelan SP Chandran K Brummelkamp TR 《Nature》2011,477(7364):340-343
Infections by the Ebola and Marburg filoviruses cause a rapidly fatal haemorrhagic fever in humans for which no approved antivirals are available. Filovirus entry is mediated by the viral spike glycoprotein (GP), which attaches viral particles to the cell surface, delivers them to endosomes and catalyses fusion between viral and endosomal membranes. Additional host factors in the endosomal compartment are probably required for viral membrane fusion; however, despite considerable efforts, these critical host factors have defied molecular identification. Here we describe a genome-wide haploid genetic screen in human cells to identify host factors required for Ebola virus entry. Our screen uncovered 67 mutations disrupting all six members of the homotypic fusion and vacuole protein-sorting (HOPS) multisubunit tethering complex, which is involved in the fusion of endosomes to lysosomes, and 39 independent mutations that disrupt the endo/lysosomal cholesterol transporter protein Niemann-Pick C1 (NPC1). Cells defective for the HOPS complex or NPC1 function, including primary fibroblasts derived from human Niemann-Pick type C1 disease patients, are resistant to infection by Ebola virus and Marburg virus, but remain fully susceptible to a suite of unrelated viruses. We show that membrane fusion mediated by filovirus glycoproteins and viral escape from the vesicular compartment require the NPC1 protein, independent of its known function in cholesterol transport. Our findings uncover unique features of the entry pathway used by filoviruses and indicate potential antiviral strategies to combat these deadly agents. 相似文献
3.
A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma 总被引:1,自引:0,他引:1
Bertolotto C Lesueur F Giuliano S Strub T de Lichy M Bille K Dessen P d'Hayer B Mohamdi H Remenieras A Maubec E de la Fouchardière A Molinié V Vabres P Dalle S Poulalhon N Martin-Denavit T Thomas L Andry-Benzaquen P Dupin N Boitier F Rossi A Perrot JL Labeille B Robert C Escudier B Caron O Brugières L Saule S Gardie B Gad S Richard S Couturier J Teh BT Ghiorzo P Pastorino L Puig S Badenas C Olsson H Ingvar C Rouleau E Lidereau R Bahadoran P Vielh P Corda E Blanché H Zelenika D 《Nature》2011,480(7375):94-98
4.
Rasmussen SG Choi HJ Fung JJ Pardon E Casarosa P Chae PS Devree BT Rosenbaum DM Thian FS Kobilka TS Schnapp A Konetzki I Sunahara RK Gellman SH Pautsch A Steyaert J Weis WI Kobilka BK 《Nature》2011,469(7329):175-180
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
5.
Fault lubrication during earthquakes 总被引:8,自引:0,他引:8
Di Toro G Han R Hirose T De Paola N Nielsen S Mizoguchi K Ferri F Cocco M Shimamoto T 《Nature》2011,471(7339):494-498
The determination of rock friction at seismic slip rates (about 1?m?s(-1)) is of paramount importance in earthquake mechanics, as fault friction controls the stress drop, the mechanical work and the frictional heat generated during slip. Given the difficulty in determining friction by seismological methods, elucidating constraints are derived from experimental studies. Here we review a large set of published and unpublished experiments (~300) performed in rotary shear apparatus at slip rates of 0.1-2.6?m?s(-1). The experiments indicate a significant decrease in friction (of up to one order of magnitude), which we term fault lubrication, both for cohesive (silicate-built, quartz-built and carbonate-built) rocks and non-cohesive rocks (clay-rich, anhydrite, gypsum and dolomite gouges) typical of crustal seismogenic sources. The available mechanical work and the associated temperature rise in the slipping zone trigger a number of physicochemical processes (gelification, decarbonation and dehydration reactions, melting and so on) whose products are responsible for fault lubrication. The similarity between (1) experimental and natural fault products and (2) mechanical work measures resulting from these laboratory experiments and seismological estimates suggests that it is reasonable to extrapolate experimental data to conditions typical of earthquake nucleation depths (7-15?km). It seems that faults are lubricated during earthquakes, irrespective of the fault rock composition and of the specific weakening mechanism involved. 相似文献
6.
ARTC1-mediated ADP-ribosylation of GRP78/BiP: a new player in endoplasmic-reticulum stress responses
7.
8.
van der Meijden PE Feijge MA Swieringa F Gilio K Nergiz-Unal R Hamulyák K Heemskerk JW 《Cellular and molecular life sciences : CMLS》2012,69(20):3481-3492
The fibrin(ogen) receptor, integrin α(IIb)β(3), has a well-established role in platelet spreading, aggregation and clot retraction. How α(IIb)β(3) contributes to platelet-dependent coagulation is less well resolved. Here, we demonstrate that the potent suppressing effect of clinically used α(IIb)β(3) blockers on tissue factor-induced thrombin generation is linked to diminished platelet Ca(2+) responses and phosphatidylserine (PS) exposure. The same blockers suppress these responses in platelets stimulated with collagen and thrombin receptor agonists, whereas added fibrinogen potentiates these responses. In platelets spreading on fibrinogen, outside-in α(IIb)β(3) signaling similarly enhances thrombin-induced Ca(2+) rises and PS exposure. These responses are reduced in α(IIb)β(3)-deficient platelets from patients with Glanzmann's thrombasthenia. Furthermore, the contribution of α(IIb)β(3) to tissue factor-induced platelet Ca(2+) rises, PS exposure and thrombin generation in plasma are fully dependent on Syk kinase activity. Tyrosine phosphorylation analysis confirms a key role of Syk activation, which is largely but not exclusively dependent on α(IIb)β(3) activation. It is concluded that the majority of tissue factor-induced procoagulant activity of platelets relies on Syk activation and ensuing Ca(2+) signal generation, and furthermore that a considerable part of Syk activation relies on α(IIb)β(3) signaling. These results hence point to a novel role of Syk in integrin-dependent thrombin generation. 相似文献
9.
Release of chromatin protein HMGB1 by necrotic cells triggers inflammation 总被引:129,自引:0,他引:129
High mobility group 1 (HMGB1) protein is both a nuclear factor and a secreted protein. In the cell nucleus it acts as an architectural chromatin-binding factor that bends DNA and promotes protein assembly on specific DNA targets. Outside the cell, it binds with high affinity to RAGE (the receptor for advanced glycation end products) and is a potent mediator of inflammation. HMGB1 is secreted by activated monocytes and macrophages, and is passively released by necrotic or damaged cells. Here we report that Hmgb1(-/-) necrotic cells have a greatly reduced ability to promote inflammation, which proves that the release of HMGB1 can signal the demise of a cell to its neighbours. Apoptotic cells do not release HMGB1 even after undergoing secondary necrosis and partial autolysis, and thus fail to promote inflammation even if not cleared promptly by phagocytic cells. In apoptotic cells, HMGB1 is bound firmly to chromatin because of generalized underacetylation of histone and is released in the extracellular medium (promoting inflammation) if chromatin deacetylation is prevented. Thus, cells undergoing apoptosis are programmed to withhold the signal that is broadcast by cells that have been damaged or killed by trauma. 相似文献
10.
Bonatti E Ligi M Brunelli D Cipriani A Fabretti P Ferrante V Gasperini L Ottolini L 《Nature》2003,423(6939):499-505
A 20-Myr record of creation of oceanic lithosphere is exposed along a segment of the central Mid-Atlantic Ridge on an uplifted sliver of lithosphere. The degree of melting of the mantle that is upwelling below the ridge, estimated from the chemistry of the exposed mantle rocks, as well as crustal thickness inferred from gravity measurements, show oscillations of approximately 3-4 Myr superimposed on a longer-term steady increase with time. The time lag between oscillations of mantle melting and crustal thickness indicates that the mantle is upwelling at an average rate of approximately 25 mm x yr(-1), but this appears to vary through time. Slow-spreading lithosphere seems to form through dynamic pulses of mantle upwelling and melting, leading not only to along-axis segmentation but also to across-axis structural variability. Also, the central Mid-Atlantic Ridge appears to have become steadily hotter over the past 20 Myr, possibly owing to north-south mantle flow. 相似文献