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101.
Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 are associated with systemic lupus erythematosus 总被引:1,自引:0,他引:1
Lee-Kirsch MA Gong M Chowdhury D Senenko L Engel K Lee YA de Silva U Bailey SL Witte T Vyse TJ Kere J Pfeiffer C Harvey S Wong A Koskenmies S Hummel O Rohde K Schmidt RE Dominiczak AF Gahr M Hollis T Perrino FW Lieberman J Hübner N 《Nature genetics》2007,39(9):1065-1067
TREX1 acts in concert with the SET complex in granzyme A-mediated apoptosis, and mutations in TREX1 cause Aicardi-Goutières syndrome and familial chilblain lupus. Here, we report monoallelic frameshift or missense mutations and one 3' UTR variant of TREX1 present in 9/417 individuals with systemic lupus erythematosus but absent in 1,712 controls (P = 4.1 x 10(-7)). We demonstrate that two mutant TREX1 alleles alter subcellular targeting. Our findings implicate TREX1 in the pathogenesis of SLE. 相似文献
102.
Zusammenfassung Voltage-clamp Versuche an markhaltigen Nervenfasern vonXenopus laevis ergaben, dass die Inaktivierung der Na-Permeabilität unter dem Einfluss von Skorpiongift extrem verlangsamt und unvollständig ist. Durch Aufspaltung der Variablenh der Ionentheorie in 2 voneinander unabhängige Komponenten kann der zeitliche Verlauf der Na-Permeabilität berechnet werden.
This work was supported by the Deutsche Forschungsgemeinschaft, Bad Godesberg. 相似文献
This work was supported by the Deutsche Forschungsgemeinschaft, Bad Godesberg. 相似文献
103.
104.
Developing an optical amplifier on silicon is essential for the success of silicon-on-insulator (SOI) photonic integrated circuits. Recently, optical gain with a 1-nm bandwidth was demonstrated using the Raman effect, which led to the demonstration of a Raman oscillator, lossless optical modulation and optically tunable slow light. A key strength of optical communications is the parallelism of information transfer and processing onto multiple wavelength channels. However, the relatively narrow Raman gain bandwidth only allows for amplification or generation of a single wavelength channel. If broad gain bandwidths were to be demonstrated on silicon, then an array of wavelength channels could be generated and processed, representing a critical advance for densely integrated photonic circuits. Here we demonstrate net on/off gain over a wavelength range of 28 nm through the optical process of phase-matched four-wave mixing in suitably designed SOI channel waveguides. We also demonstrate wavelength conversion in the range 1,511-1,591 nm with peak conversion efficiencies of +5.2 dB, which represents more than 20 times improvement on previous four-wave-mixing efficiencies in SOI waveguides. These advances allow for the implementation of dense wavelength division multiplexing in an all-silicon photonic integrated circuit. Additionally, all-optical delays, all-optical switches, optical signal regenerators and optical sources for quantum information technology, all demonstrated using four-wave mixing in silica fibres, can now be transferred to the SOI platform. 相似文献
105.
A culture of P388 murine lymphoblastoid cells has been shown to contain type C oncornavirus-like particles budding at the plasma membrane. Occasionally intracytoplasmic type A and immature type B particles were also observed by electron microscope techniques. The discovery of oncornavirus-like particles in the P388 cell line increases the utility of this neoplastic system for detecting potential antineoplastic agents. 相似文献
106.
The existence and the regulatory mechanisms of the Pasteur effect in facultative anaerobic metazoa are discussed. There are three reasons for the controversy surrounding this phenomenon.1) The different definitions of the Pasteur effect,2) the antagonistic effect of metabolic depression and its species specific response to hypoxia, as well as3) the laboratory-specific differences in the experimental procedures for analyzing the Pasteur effect and its regulation. This review aims to clarify the confusion about the existence of the Pasteur effect in facultative anaerobic metazoa and to offer possible molecular mechanisms. 相似文献
107.
Locke DP Hillier LW Warren WC Worley KC Nazareth LV Muzny DM Yang SP Wang Z Chinwalla AT Minx P Mitreva M Cook L Delehaunty KD Fronick C Schmidt H Fulton LA Fulton RS Nelson JO Magrini V Pohl C Graves TA Markovic C Cree A Dinh HH Hume J Kovar CL Fowler GR Lunter G Meader S Heger A Ponting CP Marques-Bonet T Alkan C Chen L Cheng Z Kidd JM Eichler EE White S Searle S Vilella AJ Chen Y Flicek P Ma J Raney B Suh B Burhans R Herrero J Haussler D Faria R Fernando O Darré F Farré D Gazave E Oliva M 《Nature》2011,469(7331):529-533
'Orang-utan' is derived from a Malay term meaning 'man of the forest' and aptly describes the southeast Asian great apes native to Sumatra and Borneo. The orang-utan species, Pongo abelii (Sumatran) and Pongo pygmaeus (Bornean), are the most phylogenetically distant great apes from humans, thereby providing an informative perspective on hominid evolution. Here we present a Sumatran orang-utan draft genome assembly and short read sequence data from five Sumatran and five Bornean orang-utan genomes. Our analyses reveal that, compared to other primates, the orang-utan genome has many unique features. Structural evolution of the orang-utan genome has proceeded much more slowly than other great apes, evidenced by fewer rearrangements, less segmental duplication, a lower rate of gene family turnover and surprisingly quiescent Alu repeats, which have played a major role in restructuring other primate genomes. We also describe a primate polymorphic neocentromere, found in both Pongo species, emphasizing the gradual evolution of orang-utan genome structure. Orang-utans have extremely low energy usage for a eutherian mammal, far lower than their hominid relatives. Adding their genome to the repertoire of sequenced primates illuminates new signals of positive selection in several pathways including glycolipid metabolism. From the population perspective, both Pongo species are deeply diverse; however, Sumatran individuals possess greater diversity than their Bornean counterparts, and more species-specific variation. Our estimate of Bornean/Sumatran speciation time, 400,000?years ago, is more recent than most previous studies and underscores the complexity of the orang-utan speciation process. Despite a smaller modern census population size, the Sumatran effective population size (N(e)) expanded exponentially relative to the ancestral N(e) after the split, while Bornean N(e) declined over the same period. Overall, the resources and analyses presented here offer new opportunities in evolutionary genomics, insights into hominid biology, and an extensive database of variation for conservation efforts. 相似文献
108.
Yokoyama S Woods SL Boyle GM Aoude LG MacGregor S Zismann V Gartside M Cust AE Haq R Harland M Taylor JC Duffy DL Holohan K Dutton-Regester K Palmer JM Bonazzi V Stark MS Symmons J Law MH Schmidt C Lanagan C O'Connor L Holland EA Schmid H Maskiell JA Jetann J Ferguson M Jenkins MA Kefford RF Giles GG Armstrong BK Aitken JF Hopper JL Whiteman DC Pharoah PD Easton DF Dunning AM Newton-Bishop JA Montgomery GW Martin NG Mann GJ Bishop DT Tsao H Trent JM Fisher DE Hayward NK Brown KM 《Nature》2011,480(7375):99-103
109.
Serena Stadler Chi Huu Nguyen Helga Schachner Daniela Milovanovic Silvio Holzner Stefan Brenner Julia Eichsteininger Mira Stadler Daniel Senfter Liselotte Krenn Wolfgang M. Schmidt Nicole Huttary Sigurd Krieger Oskar Koperek Zsuzsanna Bago-Horvath Konstantin Alexander Brendel Brigitte Marian Oliver de Wever Robert M. Mader Benedikt Giessrigl Walter Jäger Helmut Dolznig Georg Krupitza 《Cellular and molecular life sciences : CMLS》2017,74(10):1907-1921
Retraction of mesenchymal stromal cells supports the invasion of colorectal cancer cells (CRC) into the adjacent compartment. CRC-secreted 12(S)-HETE enhances the retraction of cancer-associated fibroblasts (CAFs) and therefore, 12(S)-HETE may enforce invasivity of CRC. Understanding the mechanisms of metastatic CRC is crucial for successful intervention. Therefore, we studied pro-invasive contributions of stromal cells in physiologically relevant three-dimensional in vitro assays consisting of CRC spheroids, CAFs, extracellular matrix and endothelial cells, as well as in reductionist models. In order to elucidate how CAFs support CRC invasion, tumour spheroid-induced CAF retraction and free intracellular Ca2+ levels were measured and pharmacological- or siRNA-based inhibition of selected signalling cascades was performed. CRC spheroids caused the retraction of CAFs, generating entry gates in the adjacent surrogate stroma. The responsible trigger factor 12(S)-HETE provoked a signal, which was transduced by PLC, IP3, free intracellular Ca2+, Ca2+-calmodulin-kinase-II, RHO/ROCK and MYLK which led to the activation of myosin light chain 2, and subsequent CAF mobility. RHO activity was observed downstream as well as upstream of Ca2+ release. Thus, Ca2+ signalling served as central signal amplifier. Treatment with the FDA-approved drugs carbamazepine, cinnarizine, nifedipine and bepridil HCl, which reportedly interfere with cellular calcium availability, inhibited CAF-retraction. The elucidation of signalling pathways and identification of approved inhibitory drugs warrant development of intervention strategies targeting tumour–stroma interaction. 相似文献
110.