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281.
Chen ST Lin YL Huang MT Wu MF Cheng SC Lei HY Lee CK Chiou TW Wong CH Hsieh SL 《Nature》2008,453(7195):672-676
Dengue haemorrhagic fever and dengue shock syndrome, the most severe responses to dengue virus (DV) infection, are characterized by plasma leakage (due to increased vascular permeability) and low platelet counts. CLEC5A (C-type lectin domain family 5, member A; also known as myeloid DAP12-associating lectin (MDL-1)) contains a C-type lectin-like fold similar to the natural-killer T-cell C-type lectin domains and associates with a 12-kDa DNAX-activating protein (DAP12) on myeloid cells. Here we show that CLEC5A interacts with the dengue virion directly and thereby brings about DAP12 phosphorylation. The CLEC5A-DV interaction does not result in viral entry but stimulates the release of proinflammatory cytokines. Blockade of CLEC5A-DV interaction suppresses the secretion of proinflammatory cytokines without affecting the release of interferon-alpha, supporting the notion that CLEC5A acts as a signalling receptor for proinflammatory cytokine release. Moreover, anti-CLEC5A monoclonal antibodies inhibit DV-induced plasma leakage, as well as subcutaneous and vital-organ haemorrhaging, and reduce the mortality of DV infection by about 50% in STAT1-deficient mice. Our observation that blockade of CLEC5A-mediated signalling attenuates the production of proinflammatory cytokines by macrophages infected with DV (either alone or complexed with an enhancing antibody) offers a promising strategy for alleviating tissue damage and increasing the survival of patients suffering from dengue haemorrhagic fever and dengue shock syndrome, and possibly even other virus-induced inflammatory diseases. 相似文献
282.
Lin Fang Jia Ye Ning Li Yong Zhang SongGang Li Gane Ka-Shu Wong Jun Wang 《科学通报(英文版)》2008,53(5):746-750
Positive correlation between recombination rate and nucleoUde diversity has been observed in a wide variety of eukaryotes on megabase scale. On the basis of genome-wide chicken genetic variation map generated by comparing three domestic breeds with wild ancestor and the positions of markers on the genetic linkage map, we found that SNPs rates were similar for all chromosomes while the recombination rates increased in micro chromosomes. In other words no correlation exists in chromosome size. Nevertheless, when we scanned the genome by calculating the values of each characteristic within non-overlapping windows, instead of single value for each chromosomes, the nucleoUde diversity was found to be significantly correlated with the recombination rate (r=0.27, P〈0.0005). Furthermore, the significant association not only existed between these two features, but also existed between all 6 pairwise combinations of nucleoUde diversity, recombination rate, GC content and average gene length. This co-variation is very meaningful for the studies of sequence evolution. 相似文献
283.
Pian E Mazzali PA Masetti N Ferrero P Klose S Palazzi E Ramirez-Ruiz E Woosley SE Kouveliotou C Deng J Filippenko AV Foley RJ Fynbo JP Kann DA Li W Hjorth J Nomoto K Patat F Sauer DN Sollerman J Vreeswijk PM Guenther EW Levan A O'Brien P Tanvir NR Wijers RA Dumas C Hainaut O Wong DS Baade D Wang L Amati L Cappellaro E Castro-Tirado AJ Ellison S Frontera F Fruchter AS Greiner J Kawabata K Ledoux C Maeda K Møller P Nicastro L Rol E Starling R 《Nature》2006,442(7106):1011-1013
Long-duration gamma-ray bursts (GRBs) are associated with type Ic supernovae that are more luminous than average and that eject material at very high velocities. Less-luminous supernovae were not hitherto known to be associated with GRBs, and therefore GRB-supernovae were thought to be rare events. Whether X-ray flashes--analogues of GRBs, but with lower luminosities and fewer gamma-rays--can also be associated with supernovae, and whether they are intrinsically 'weak' events or typical GRBs viewed off the axis of the burst, is unclear. Here we report the optical discovery and follow-up observations of the type Ic supernova SN 2006aj associated with X-ray flash XRF 060218. Supernova 2006aj is intrinsically less luminous than the GRB-supernovae, but more luminous than many supernovae not accompanied by a GRB. The ejecta velocities derived from our spectra are intermediate between these two groups, which is consistent with the weakness of both the GRB output and the supernova radio flux. Our data, combined with radio and X-ray observations, suggest that XRF 060218 is an intrinsically weak and soft event, rather than a classical GRB observed off-axis. This extends the GRB-supernova connection to X-ray flashes and fainter supernovae, implying a common origin. Events such as XRF 060218 are probably more numerous than GRB-supernovae. 相似文献
284.
Okada A Charron F Morin S Shin DS Wong K Fabre PJ Tessier-Lavigne M McConnell SK 《Nature》2006,444(7117):369-373
In the spinal cord, sonic hedgehog (Shh) is secreted by the floor plate to control the generation of distinct classes of ventral neurons along the dorsoventral axis. Genetic and in vitro studies have shown that Shh also later acts as a midline-derived chemoattractant for commissural axons. However, the receptor(s) responsible for Shh attraction remain unknown. Here we show that two Robo-related proteins, Boc and Cdon, bind specifically to Shh and are therefore candidate receptors for the action of Shh as an axon guidance ligand. Boc is expressed by commissural neurons, and targeted disruption of Boc in mouse results in the misguidance of commissural axons towards the floor plate. RNA-interference-mediated knockdown of Boc impairs the ability of rat commissural axons to turn towards an ectopic source of Shh in vitro. Taken together, these data suggest that Boc is essential as a receptor for Shh in commissural axon guidance. 相似文献
285.
A complete sequence and comparative analysis of a SARS-associated virus (Isolate BJO1) 总被引:16,自引:0,他引:16
QINE'de ZHUQingyu YUMan FANBaochang CHANGGuohui SIBingyin YANGBao'an PENGWenming JIANGTao LIUBohua DENGYongqiang LIUHong ZHANGYu WANGCui'e LIYuquan GANYonghua LIXiaoyu LUFushuang TANGang CAOWuchun YANGRuifu WANGJian LIWei XUZuyuan LIYan WUQingfa LINWei CHENWeijun TANGLin DENGYajun HANYujun LIChangfeng LEIMeng LIGuoqing LIWenjie LUHong SHIJianping TONGZongzhong ZHANGFeng LISonggang LIUBin LIUSiqi DONGWei WANGJun GaneK-SWong YUJun YANGHuanming 《科学通报(英文版)》2003,48(10):941-948
The genome sequence of the Severe Acute Respiratory Syndrome (SARS)-assoclated virus provides essential information for the identification of pathogen(s), exploration of etiology and evolution, interpretation of transmission and pathogenesis, development of diagnostics, prevention by future vaccination, and treatment by developing new drugs.We report the complete genome sequence and comparative analysis of an isolate (B J01) of the coronavirus that has been recognized as a pathogen for SARS. The genome is 29725 nt in size and has 11 ORFs (Open Reading Frames). It is composed of a stable region encoding an RNA-dependent RNA polymerase (composed of 20RFs) and a variable region representing 4 CDSs (coding sequences) for viral structural genes (the S, E, M, N proteins) and 5 PUPs (putative uncharacterized proteins). Its gene order is identical to that of other known coronaviruses. The sequence alignment with all known RNA viruses places this virus as a member in the family of Coronaviridae. Thirty putative substitutions have been identified by comparative analysis of the 5 SARS-associated virus genome sequences in GenBank. Fifteen of them lead to possible amino acid changes (non-synonymous mutations) in the proteins. Three amino acid changes, with predicted alteration of physical and chemical features, have been detected in the S protein that is postulated to be involved in the immunoreactions between the virus and its host.Two amino acid changes have been detected in the M protein,which could be related to viral envelope formation. Phylogenetic analysis suggests the possibility of non-human origin of the SARS-associated viruses but provides no evidence that they are man-made. Further efforts should focus on identifying the etiology of the SARS-associated virus and ruling out conclusively the existence of other possible SARS-related pathogen(s). 相似文献
286.
用于集成超声传感阵列的PVDF—MOSFET新结构 总被引:1,自引:0,他引:1
本文报道一种用聚酰亚胺膜垫高扩展栅的聚偏氟乙烯压电膜-MOS晶体管传感器单元结构。和一般POSFET结构相比。这种新结构大大减少了扩展栅电容,明显地提高了器件灵敏度。详述了这种结构的制造过程,特别是PI膜制备条件对CEG和器件性能的影响。 相似文献
287.
Optimization of Time-Varying Parking Charges and Parking Supply in Networks with Multiple User Classes and Multiple Parking Facilities 总被引:3,自引:0,他引:3
The optimization of parking charges and parking supply over the time of a day is an important problem in the design of transportation networks. This paper presents a bilevel model to determine the opti-mal time-varying parking charges and parking supply in road networks with multiple user classes and different types of parking facilities. The upper level of the model aims to maximize the network net benefit in response to the parking charges and parking supply, whereas the lower level is a time-dependent network equilibrium problem with elastic demand. A descent-gradient-based solution algorithm is adapted to solve the model. The numerical results show that the implementation of time-varying parking charges and parking supply is useful to effectively cater to the time-varying demand with different parking needs. The model provides a powerful tool for strategically designing parking locations and evaluating various parking policies. 相似文献
288.
Gerlach B Cordier SM Schmukle AC Emmerich CH Rieser E Haas TL Webb AI Rickard JA Anderton H Wong WW Nachbur U Gangoda L Warnken U Purcell AW Silke J Walczak H 《Nature》2011,471(7340):591-596
Members of the tumour necrosis factor (TNF) receptor superfamily have important functions in immunity and inflammation. Recently linear ubiquitin chains assembled by a complex containing HOIL-1 and HOIP (also known as RBCK1 and RNF31, respectively) were implicated in TNF signalling, yet their relevance in vivo remained uncertain. Here we identify SHARPIN as a third component of the linear ubiquitin chain assembly complex, recruited to the CD40 and TNF receptor signalling complexes together with its other constituents, HOIL-1 and HOIP. Mass spectrometry of TNF signalling complexes revealed RIP1 (also known as RIPK1) and NEMO (also known as IKKγ or IKBKG) to be linearly ubiquitinated. Mutation of the Sharpin gene (Sharpin(cpdm/cpdm)) causes chronic proliferative dermatitis (cpdm) characterized by inflammatory skin lesions and defective lymphoid organogenesis. Gene induction by TNF, CD40 ligand and interleukin-1β was attenuated in cpdm-derived cells which were rendered sensitive to TNF-induced death. Importantly, Tnf gene deficiency prevented skin lesions in cpdm mice. We conclude that by enabling linear ubiquitination in the TNF receptor signalling complex, SHARPIN interferes with TNF-induced cell death and, thereby, prevents inflammation. Our results provide evidence for the relevance of linear ubiquitination in vivo in preventing inflammation and regulating immune signalling. 相似文献