全文获取类型
收费全文 | 300篇 |
免费 | 33篇 |
出版年
2020年 | 3篇 |
2018年 | 2篇 |
2016年 | 6篇 |
2015年 | 3篇 |
2014年 | 11篇 |
2013年 | 2篇 |
2012年 | 9篇 |
2011年 | 12篇 |
2010年 | 12篇 |
2009年 | 8篇 |
2008年 | 14篇 |
2007年 | 10篇 |
2006年 | 11篇 |
2005年 | 9篇 |
2004年 | 13篇 |
2003年 | 8篇 |
2002年 | 7篇 |
2001年 | 7篇 |
2000年 | 8篇 |
1999年 | 4篇 |
1998年 | 11篇 |
1997年 | 8篇 |
1996年 | 4篇 |
1995年 | 5篇 |
1994年 | 4篇 |
1993年 | 2篇 |
1992年 | 6篇 |
1991年 | 13篇 |
1990年 | 13篇 |
1989年 | 13篇 |
1988年 | 9篇 |
1987年 | 12篇 |
1986年 | 6篇 |
1985年 | 9篇 |
1984年 | 5篇 |
1983年 | 7篇 |
1982年 | 11篇 |
1981年 | 5篇 |
1980年 | 4篇 |
1977年 | 3篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1972年 | 1篇 |
1971年 | 4篇 |
1970年 | 3篇 |
1969年 | 2篇 |
1967年 | 1篇 |
1966年 | 2篇 |
1961年 | 1篇 |
1903年 | 1篇 |
排序方式: 共有333条查询结果,搜索用时 265 毫秒
21.
We have used carbon-fibre amperometry to examine the kinetics of individual secretory granule fusion/release events in bovine adrenal chromaffin cells. Transfection with plasmids encoding the light chains of botulinum neurotoxins (BoNTs) was used to investigate the effects of cleavage of syntaxin or SNAP-25 on exocytosis. Expression of BoNT/C1 or BoNT/E inhibited the extent of exocytosis that was evoked by application of digitonin/Ca(2+) to permeabilise and stimulate single chromaffin cells. Following neurotoxin expression, the residual release events were no different from those of control cells in their magnitude and kinetics from analysis of the amperometric spikes. In contrast, activation of protein kinase C (PKC) resulted in a modification of the kinetics of single granule release events. Following phorbol ester treatment, the amperometric spikes showed a significant decrease in their total charge due to a decrease in their mean half-width with increases in the rate of the initial rise and also the fall to baseline of the spikes. These changes were prevented by pre-treatment with the PKC inhibitor bisindolylmaleimide. These results suggest that PKC regulates the rate of fusion pore expansion and also subsequent pore closure or granule retrieval. A PKC-mediated regulation of kiss-and-run fusion may, therefore, control the extent of catecholamine release from single secretory granules. The experimental approach used here may provide further information on the protein constituents and regulation of the fusion pore machinery. 相似文献
22.
Neuronal Ca2+ sensor-1/frequenin functions in an autocrine pathway regulating Ca2+ channels in bovine adrenal chromaffin cells 总被引:1,自引:0,他引:1
NCS-1/frequenin belongs to a family of EF-hand-containing Ca(2+) sensors expressed mainly in neurons. Overexpression of NCS-1/frequenin has been shown to stimulate neurotransmitter release but little else is known of its cellular roles. We have constructed an EF-hand mutant, NCS-1(E120Q), as a likely dominant inhibitor of cellular NCS-1 function. Recombinant NCS-1(E120Q) showed an impaired Ca(2+)-dependent conformational change but could still bind to cellular proteins. Transient expression of this mutant, but not NCS-1, in bovine adrenal chromaffin cells increased non-L-type Ca(2+) channel currents. Cells expressing NCS-1(E120Q) no longer responded effectively to the removal of autocrine purinergic/opioid inhibition of Ca(2+) currents but still showed voltage-dependent facilitation. These data are consistent with the existence of both voltage-dependent and voltage-independent pathways for Ca(2+) channel inhibition in chromaffin cells. Our results suggest a novel function for NCS-1 specific for the voltage-independent autocrine pathway that negatively regulates non-L-type Ca(2+) channels in chromaffin cells. 相似文献
23.
Cysteine-string protein (Csp) is a major synaptic vesicle and secretory granule protein first discovered in Drosophila and Torpedo. Csps were subsequently identified from Xenopus, Caenorhabditis elegans, and mammalian species. It is clear from the study of a null mutant in Drosophila that Csp is required for viability of the organism and that it has a key role in neurotransmitter release. In addition, other studies have directly implicated Csp in regulated exocytosis in mammalian neuroendocrine and endocrine cell types, and its distribution suggests a general role in regulated exocytosis. An early hypothesis was that Csp functioned in the control of voltage-gated Ca2+ channels. Csp, however, must have an additional function as a direct regulator of the exocytotic machinery as changes in Csp expression modify the extent of exocytosis triggered directly by Ca2+ in permeabilised cells. Csps possess a cysteine-string domain that is highly palmitoylated and confers membrane targeting. In addition, Csps have a conserved "J" domain that mediates binding to an activation of the Hsp70/ Hsc70 chaperone ATPases. This and other evidence implicate Csps as molecular chaperones in the synapse that are likely to control the correct conformational folding of one or more components of the vesicular exocytotic machinery. Targets for Csp include the vesicle protein VAMP/synaptobrevin and the plasma membrane protein syntaxin 1, the significance of which is discussed in possible models to account for current knowledge of Csp function. 相似文献
24.
Interest in the use of low-copy nuclear genes for phylogenetic analyses of
plants has grown rapidly, because highly repetitive genes such as those
commonly used are limited in number. Furthermore, because low- copy genes
are subject to different evolutionary processes than are plastid genes or
highly repetitive nuclear markers, they provide a valuable source of
independent phylogenetic evidence. The gene for granule-bound starch
synthase (GBSSI or waxy) exists in a single copy in nearly all plants
examined so far. Our study of GBSSI had three parts: (1) Amino acid
sequences were compared across a broad taxonomic range, including grasses,
four dicotyledons, and the microbial homologs of GBSSI. Inferred structural
information was used to aid in the alignment of these very divergent
sequences. The informed alignments highlight amino acids that are conserved
across all sequences, and demonstrate that structural motifs can be highly
conserved in spite of marked divergence in amino acid sequence. (2)
Maximum-likelihood (ML) analyses were used to examine exon sequence
evolution throughout grasses. Differences in probabilities among
substitution types and marked among-site rate variation contributed to the
observed pattern of variation. Of the parameters examined in our set of
likelihood models, the inclusion of among-site rate variation following a
gamma distribution caused the greatest improvement in likelihood score. (3)
We performed cladistic parsimony analyses of GBSSI sequences throughout
grasses, within tribes, and within genera to examine the phylogenetic
utility of the gene. Introns provide useful information among very closely
related species, but quickly become difficult to align among more divergent
taxa. Exons are variable enough to provide extensive resolution within the
family, but with low bootstrap support. The combined results of amino acid
sequence comparisons, maximum-likelihood analyses, and phylogenetic studies
underscore factors that might affect phylogenetic reconstruction. In this
case, accommodation of the variable rate of evolution among sites might be
the first step in maximizing the phylogenetic utility of GBSSI.
相似文献
25.
Royo H Polikiewicz G Mahadevaiah SK Prosser H Mitchell M Bradley A de Rooij DG Burgoyne PS Turner JM 《Current biology : CB》2010,20(23):2117-2123
The mammalian X and Y chromosomes share little homology and are largely unsynapsed during normal meiosis. This asynapsis triggers inactivation of X- and Y-linked genes, or meiotic sex chromosome inactivation (MSCI). Whether MSCI is essential for male meiosis is unclear. Pachytene arrest and apoptosis is observed in mouse mutants in which MSCI fails, e.g., Brca1(-/-), H2afx(-/-), Sycp1(-/-), and Msh5(-/-). However, these also harbor defects in synapsis and/or recombination and as such may activate a putative pachytene checkpoint. Here we present evidence that MSCI failure is sufficient to cause pachytene arrest. XYY males exhibit Y-Y synapsis and Y chromosomal escape from MSCI without accompanying synapsis/recombination defects. We find that XYY males, like synapsis/recombination mutants, display pachytene arrest and that this can be circumvented by preventing Y-Y synapsis and associated Y gene expression. Pachytene expression of individual Y genes inserted as transgenes on autosomes shows that expression of the Zfy 1/2 paralogs in XY males is sufficient to phenocopy the pachytene arrest phenotype; insertion of Zfy 1/2 on the X chromosome where they are subject to MSCI prevents this response. Our findings show that MSCI is essential for male meiosis and, as such, provide insight into the differential severity of meiotic mutations' effects on male and female meiosis. 相似文献
26.
Background
If biology is modular then clusters, or communities, of proteins derived using only protein interaction network structure should define protein modules with similar biological roles. We investigate the link between biological modules and network communities in yeast and its relationship to the scale at which we probe the network. 相似文献27.
G. Martinez-Garcia A.C. Johnson R.T. Bachmann C.J. Williams A. Burgoyne R.G.J. Edyvean 《International biodeterioration & biodegradation》2007,59(4):273-282
Olive mill wastewater (OMW) is a highly polluting wastewater, caused by a high organic load and phenol content. These characteristics suggest that it may be suitable for aerobic treatment and anaerobic bacterial digestion. Aerobic treatment coupled with anaerobic bacterial digestion may be economically feasible as the methane produced is a valuable energy source while simultaneously purifying the OMW. In an attempt to improve the overall performance of the process, the addition of a co-substrate such as whey to the aerobic treatment pre-treatment of OMW by the yeast Candida tropicalis was studied.The two-stage system operated satisfactorily up to an organic loading rate (OLR) of 3.0 kg COD L−1 day−1 with a biogas production rate of 1.25 Lbiogas Lreactor−1 day−1 and a total COD reduction in excess of 93% (62% COD reduction in aerobic pretreatment and 83% COD reduction in anaerobic digestion). Fifty-four percent of the phenol was biodegraded during the aerobic treatment stage, and biogas with between 68% and 75% methane was produced during anaerobic digestion. 相似文献
28.
Dayani Rajamanoharan Hannah V. McCue Robert D. Burgoyne Lee P. Haynes 《Molecular biology of the cell》2015,26(8):1428-1439
Calcium and phosphoinositide signaling regulate cell division in model systems, but their significance in mammalian cells is unclear. Calcium-binding protein-7 (CaBP7) is a phosphatidylinositol 4-kinaseIIIβ (PI4KIIIβ) inhibitor required during cytokinesis in mammalian cells, hinting at a link between these pathways. Here we characterize a novel association of CaBP7 with lysosomes that cluster at the intercellular bridge during cytokinesis in HeLa cells. We show that CaBP7 regulates lysosome clustering and that PI4KIIIβ is essential for normal cytokinesis. CaBP7 depletion induces lysosome mislocalization, extension of intercellular bridge lifetime, and cytokinesis failure. These data connect phosphoinositide and calcium pathways to lysosome localization and normal cytokinesis in mammalian cells. 相似文献
29.
Distel DL Amin M Burgoyne A Linton E Mamangkey G Morrill W Nove J Wood N Yang J 《Molecular phylogenetics and evolution》2011,61(2):245-254
The ability to consume wood as food (xylotrophy) is unusual among animals. In terrestrial environments, termites and other xylotrophic insects are the principle wood consumers while in marine environments wood-boring bivalves fulfill this role. However, the evolutionary origin of wood feeding in bivalves has remained largely unexplored. Here we provide data indicating that xylotrophy has arisen just once in Bivalvia in a single wood-feeding bivalve lineage that subsequently diversified into distinct shallow- and deep-water branches, both of which have been broadly successful in colonizing the world’s oceans. These data also suggest that the appearance of this remarkable life habit was approximately coincident with the acquisition of bacterial endosymbionts. Here we generate a robust phylogeny for xylotrophic bivalves and related species based on sequences of small and large subunit nuclear rRNA genes. We then trace the distribution among the modern taxa of morphological characters and character states associated with xylotrophy and xylotrepesis (wood-boring) and use a parsimony-based method to infer their ancestral states. Based on these ancestral state reconstructions we propose a set of plausible hypotheses describing the evolution of symbiotic xylotrophy in Bivalvia. Within this context, we reinterpret one of the most remarkable progressions in bivalve evolution, the transformation of the “typical” myoid body plan to create a unique lineage of worm-like, tube-forming, wood-feeding clams. The well-supported phylogeny presented here is inconsistent with most taxonomic treatments for xylotrophic bivalves, indicating that the bivalve family Pholadidae and the subfamilies Teredininae and Bankiinae of the family Teredinidae are non-monophyletic, and that the principle traits used for their taxonomic diagnosis are phylogenetically misleading. 相似文献
30.
Hall GL Logie KM Parsons F Schulzke SM Nolan G Murray C Ranganathan S Robinson P Sly PD Stick SM;AREST CF Berry L Garratt L Massie J Mott L Poreddy S Simpson S 《PloS one》2011,6(8):e23932