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91.
In De magnete (1600), Gilbert frequently appealed to diagrams. As result of a focus on the experimental methodology of the treatise, its diagrammatic dimension has been overlooked in the scholarship. This paper argues that, in De magnete, at least some diagrams are epistemically relevant; specifically, Gilbert moves from experiments to concepts and theories through diagrams. To show this, I analyze the role that the “Diagram of motions in magnetick orbes” plays in the formulation of Gilbert's rule of alignment of magnetic bodies within the orb of virtue (the space around a magnet where its influence is exerted). If it turns out that diagrams play a genuine role in Gilbert's magnetic investigations, then his investigative strategy goes beyond mere experimentalism. 相似文献
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In this paper we evaluated traffic characteristics and vegetation and topographic features associated with mule deer kills on 3 highways (US 40, SR 32, SR 248) in northeastern Utah. We also compared number, and sex and age composition of roadkills to that of the living population observed during spotlight counts. From 15 October 1991 to 14 October 1993 we documented 397 deer roadkills: 51.6% were does, 18.9% bucks, 21.7% fawns, and 7.8% could not be classified. Sixty-seven percent of adult kills were 2.5 yr of age. Kill composition compared closely to spotlight counts. Of 1515 spotlight deer, 65.2% were does, 8.9% bucks, and 25.9% fawns. Spotlight density and deer mortality were strongly correlated from summer 1992 through summer 1993 ( r = 0.94). Traffic conditions, topographic features, and vegetative characteristics contributed to mortality levels. Roadkills were highest along US 40 (68% year 1, 55% year 2) where traffic volume and speed were significantly higher along either state route. Large drainages intersected highways in 78% of designated kill zones. Roads adjacent to agricultural areas along all routes sustained the fewest highway mortalities. Percent cover was higher (40%) in kill zones than in other areas (29%). 相似文献
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Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter 总被引:2,自引:0,他引:2
Baughman JM Perocchi F Girgis HS Plovanich M Belcher-Timme CA Sancak Y Bao XR Strittmatter L Goldberger O Bogorad RL Koteliansky V Mootha VK 《Nature》2011,476(7360):341-345
Mitochondria from diverse organisms are capable of transporting large amounts of Ca(2+) via a ruthenium-red-sensitive, membrane-potential-dependent mechanism called the uniporter. Although the uniporter's biophysical properties have been studied extensively, its molecular composition remains elusive. We recently used comparative proteomics to identify MICU1 (also known as CBARA1), an EF-hand-containing protein that serves as a putative regulator of the uniporter. Here, we use whole-genome phylogenetic profiling, genome-wide RNA co-expression analysis and organelle-wide protein coexpression analysis to predict proteins functionally related to MICU1. All three methods converge on a novel predicted transmembrane protein, CCDC109A, that we now call 'mitochondrial calcium uniporter' (MCU). MCU forms oligomers in the mitochondrial inner membrane, physically interacts with MICU1, and resides within a large molecular weight complex. Silencing MCU in cultured cells or in vivo in mouse liver severely abrogates mitochondrial Ca(2+) uptake, whereas mitochondrial respiration and membrane potential remain fully intact. MCU has two predicted transmembrane helices, which are separated by a highly conserved linker facing the intermembrane space. Acidic residues in this linker are required for its full activity. However, an S259A point mutation retains function but confers resistance to Ru360, the most potent inhibitor of the uniporter. Our genomic, physiological, biochemical and pharmacological data firmly establish MCU as an essential component of the mitochondrial Ca(2+) uniporter. 相似文献
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Mammalian Toll-like receptors (TLRs) 3, 7, 8 and 9 initiate immune responses to infection by recognizing microbial nucleic acids; however, these responses come at the cost of potential autoimmunity owing to inappropriate recognition of self nucleic acids. The localization of TLR9 and TLR7 to intracellular compartments seems to have a role in facilitating responses to viral nucleic acids while maintaining tolerance to self nucleic acids, yet the cell biology regulating the transport and localization of these receptors remains poorly understood. Here we define the route by which TLR9 and TLR7 exit the endoplasmic reticulum and travel to endolysosomes in mouse macrophages and dendritic cells. The ectodomains of TLR9 and TLR7 are cleaved in the endolysosome, such that no full-length protein is detectable in the compartment where ligand is recognized. Notably, although both the full-length and cleaved forms of TLR9 are capable of binding ligand, only the processed form recruits MyD88 on activation, indicating that this truncated receptor, rather than the full-length form, is functional. Furthermore, conditions that prevent receptor proteolysis, including forced TLR9 surface localization, render the receptor non-functional. We propose that ectodomain cleavage represents a strategy to restrict receptor activation to endolysosomal compartments and prevent TLRs from responding to self nucleic acids. 相似文献