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71.
Sara B. Seidelmann Janet K. Lighthouse Daniel M. Greif 《Cellular and molecular life sciences : CMLS》2014,71(11):1977-1999
Arteries consist of an inner single layer of endothelial cells surrounded by layers of smooth muscle and an outer adventitia. The majority of vascular developmental studies focus on the construction of endothelial networks through the process of angiogenesis. Although many devastating vascular diseases involve abnormalities in components of the smooth muscle and adventitia (i.e., the vascular wall), the morphogenesis of these layers has received relatively less attention. Here, we briefly review key elements underlying endothelial layer formation and then focus on vascular wall development, specifically on smooth muscle cell origins and differentiation, patterning of the vascular wall, and the role of extracellular matrix and adventitial progenitor cells. Finally, we discuss select human diseases characterized by marked vascular wall abnormalities. We propose that continuing to apply approaches from developmental biology to the study of vascular disease will stimulate important advancements in elucidating disease mechanism and devising novel therapeutic strategies. 相似文献
72.
Lukas M. Verburgt 《Annals of science》2016,73(1):40-67
This paper provides a detailed account of the period of the complex history of British algebra and geometry between the publication of George Peacock's Treatise on Algebra in 1830 and William Rowan Hamilton's paper on quaternions of 1843. During these years, Duncan Farquharson Gregory and William Walton published several contributions on ‘algebraical geometry’ and ‘geometrical algebra’ in the Cambridge Mathematical Journal. These contributions enabled them not only to generalize Peacock's symbolical algebra on the basis of geometrical considerations, but also to initiate the attempts to question the status of Euclidean space as the arbiter of valid geometrical interpretations. At the same time, Gregory and Walton were bound by the limits of symbolical algebra that they themselves made explicit; their work was not and could not be the ‘abstract algebra’ and ‘abstract geometry’ of figures such as Hamilton and Cayley. The central argument of the paper is that an understanding of the contributions to ‘algebraical geometry’ and ‘geometrical algebra’ of the second generation of ‘scientific’ symbolical algebraists is essential for a satisfactory explanation of the radical transition from symbolical to abstract algebra that took place in British mathematics in the 1830s–1840s. 相似文献
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76.
The effect of Si on the austenite stabilization, martensite morphology, and magnetic properties in Fe-26%Ni-x%Si (x=3.5, 5, and 6) alloys have been studied by means of transmission electron microscopy (TEM) and M?ssbauer spectroscopy techniques. TEM observations reveal that the martensite morphology is closely dependent on the Si content. The volume fraction changes of martensite and austenite phases, the hyperfine magnetic field, and isomer shift values have been determined by Mssbauer spectroscopy. The M?ssbauer study reveals that the hyperfine magnetic field, the isomer shift values and the volume fraction of martensite decrease with increasing Si content. 相似文献
77.
In higher vertebrates, sulfatases belong to a conserved family of enzymes that are involved in the regulation of cell metabolism
and in developmental cell signaling. They cleave the sulfate from sulfate esters contained in hormones, proteins, and complex
macromolecules. A highly conserved cysteine in their active site is post-translationally converted into formylglycine by the
formylglycine-generating enzyme encoded by SUMF1 (sulfatase modifying factor 1). This post-translational modification activates all sulfatases. Sulfatases are extensively
glycosylated proteins and some of them follow trafficking pathways through cells, being secreted and taken up by distant cells.
Many proteoglycans, glycoproteins, and glycolipids contain sulfated carbohydrates, which are sulfatase substrates. Indeed,
sulfatases operate as decoding factors for a large amount of biological information contained in the structures of the sulfated
sugar chains that are covalently linked to proteins and lipids. Modifications to these sulfate groups have pivotal roles in
modulating specific signaling pathways and cell metabolism in mammals. 相似文献
78.
主要探讨中药制剂四生散对人肺癌A5 4 9细胞株的增殖抑制作用以及其急性毒性.应用改进的MTT法测定四生散对肺癌细胞增殖的影响;采用琼脂糖凝胶电泳测定四生散对诱导肿瘤细胞凋亡的影响;再用分剂量组灌胃小鼠的方法,鉴定四生散的急性毒性.实验结果表明,四生散对人肺癌A5 4 9细胞株的增殖有较强的抑制作用,并具有明显的量效和时效相关性;经四生散处理后的A5 4 9细胞呈现凋亡特征性电泳条带;在3 2倍于人的剂量时,小鼠饮食和体重均在正常水平,并无异常,证实口服四生散无急性毒性. 相似文献
79.
Roscioli T Kamsteeg EJ Buysse K Maystadt I van Reeuwijk J van den Elzen C van Beusekom E Riemersma M Pfundt R Vissers LE Schraders M Altunoglu U Buckley MF Brunner HG Grisart B Zhou H Veltman JA Gilissen C Mancini GM Delrée P Willemsen MA Ramadža DP Chitayat D Bennett C Sheridan E Peeters EA Tan-Sindhunata GM de Die-Smulders CE Devriendt K Kayserili H El-Hashash OA Stemple DL Lefeber DJ Lin YY van Bokhoven H 《Nature genetics》2012,44(5):581-585
Walker-Warburg syndrome (WWS) is an autosomal recessive multisystem disorder characterized by complex eye and brain abnormalities with congenital muscular dystrophy (CMD) and aberrant a-dystroglycan glycosylation. Here we report mutations in the ISPD gene (encoding isoprenoid synthase domain containing) as the second most common cause of WWS. Bacterial IspD is a nucleotidyl transferase belonging to a large glycosyltransferase family, but the role of the orthologous protein in chordates is obscure to date, as this phylum does not have the corresponding non-mevalonate isoprenoid biosynthesis pathway. Knockdown of ispd in zebrafish recapitulates the human WWS phenotype with hydrocephalus, reduced eye size, muscle degeneration and hypoglycosylated a-dystroglycan. These results implicate ISPD in a-dystroglycan glycosylation in maintaining sarcolemma integrity in vertebrates. 相似文献
80.
Bolin C Boudra MT Fernet M Vaslin L Pennaneach V Zaremba T Biard D Cordelières FP Favaudon V Mégnin-Chanet F Hall J 《Cellular and molecular life sciences : CMLS》2012,69(6):951-962
Cyclin-dependent kinase 5 (Cdk5) has been identified as a determinant of sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. Here, the consequences of its depletion on cell survival, PARP activity, the recruitment of base excision repair (BER) proteins to DNA damage sites, and overall DNA single-strand break (SSB) repair were investigated using isogenic HeLa stably depleted (KD) and Control cell lines. Synthetic lethality achieved by disrupting PARP activity in Cdk5-deficient cells was confirmed, and the Cdk5KD cells were also found to be sensitive to the killing effects of ionizing radiation (IR) but not methyl methanesulfonate or neocarzinostatin. The recruitment profiles of GFP-PARP-1 and XRCC1-YFP to sites of micro-irradiated Cdk5KD cells were slower and reached lower maximum values, while the profile of GFP-PCNA recruitment was faster and attained higher maximum values compared to Control cells. Higher basal, IR, and hydrogen peroxide-induced polymer levels were observed in Cdk5KD compared to Control cells. Recruitment of GFP-PARP-1 in which serines 782, 785, and 786, potential Cdk5 phosphorylation targets, were mutated to alanines in micro-irradiated Control cells was also reduced. We hypothesize that Cdk5-dependent PARP-1 phosphorylation on one or more of these serines results in an attenuation of its ribosylating activity facilitating persistence at DNA damage sites. Despite these deficiencies, Cdk5KD cells are able to effectively repair SSBs probably via the long patch BER pathway, suggesting that the enhanced radiation sensitivity of Cdk5KD cells is due to a role of Cdk5 in other pathways or the altered polymer levels. 相似文献