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排序方式: 共有223条查询结果,搜索用时 31 毫秒
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Tyrosine phosphorylation of Munc18‐1 inhibits synaptic transmission by preventing SNARE assembly 下载免费PDF全文
Marieke Meijer Bernhard Dörr Hanna CA Lammertse Chrysanthi Blithikioti Jan RT van Weering Ruud FG Toonen Thomas H Söllner Matthijs Verhage 《The EMBO journal》2018,37(2):300-320
Tyrosine kinases are important regulators of synaptic strength. Here, we describe a key component of the synaptic vesicle release machinery, Munc18‐1, as a phosphorylation target for neuronal Src family kinases (SFKs). Phosphomimetic Y473D mutation of a SFK phosphorylation site previously identified by brain phospho‐proteomics abolished the stimulatory effect of Munc18‐1 on SNARE complex formation (“SNARE‐templating”) and membrane fusion in vitro. Furthermore, priming but not docking of synaptic vesicles was disrupted in hippocampal munc18‐1‐null neurons expressing Munc18‐1Y473D. Synaptic transmission was temporarily restored by high‐frequency stimulation, as well as by a Munc18‐1 mutation that results in helix 12 extension, a critical conformational step in vesicle priming. On the other hand, expression of non‐phosphorylatable Munc18‐1 supported normal synaptic transmission. We propose that SFK‐dependent Munc18‐1 phosphorylation may constitute a potent, previously unknown mechanism to shut down synaptic transmission, via direct occlusion of a Synaptobrevin/VAMP2 binding groove and subsequent hindrance of conformational changes in domain 3a responsible for vesicle priming. This would strongly interfere with the essential post‐docking SNARE‐templating role of Munc18‐1, resulting in a largely abolished pool of releasable synaptic vesicles. 相似文献
45.
铁皮石斛的离体开花 总被引:9,自引:0,他引:9
铁皮石斛(Dendrobium candidum),为一种野生兰科植物,在栽培条件下,从种子萌发到开花通常需要3~4a.研究了多种植物激素和多胺对该种石斛组织培养中花芽形成的影响,结果表明在培养基中加入合适浓度的亚精胺(spermidine)或BA(6-苄基腺嘌呤),或同时加入NAA(萘乙酸)和BA均可诱导原球茎或由之形成的无根小苗在3~6个月开花,频率在31.6%~45.8%.当将原球茎在加有ABA(脱落酸)的培养基上预培养后再移到加有BA的培养基上,花芽形成的频率可提高到平均达82.8%(个别实验中可达100%),这种诱导提早开花的现象也与实验材料的发育阶段(原球茎、无根小苗、已生根的小苗)有关,通常发生在根的形成受到完全或部分抑制的情况中. 相似文献
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47.
Efficiencies of different genes and different tree-building methods in recovering a known vertebrate phylogeny 总被引:24,自引:6,他引:18
The relative efficiencies of different protein-coding genes of the
mitochondrial genome and different tree-building methods in recovering a
known vertebrate phylogeny (two whale species, cow, rat, mouse, opossum,
chicken, frog, and three bony fish species) was evaluated. The
tree-building methods examined were the neighbor joining (NJ), minimum
evolution (ME), maximum parsimony (MP), and maximum likelihood (ML), and
both nucleotide sequences and deduced amino acid sequences were analyzed.
Generally speaking, amino acid sequences were better than nucleotide
sequences in obtaining the true tree (topology) or trees close to the true
tree. However, when only first and second codon positions data were used,
nucleotide sequences produced reasonably good trees. Among the 13 genes
examined, Nd5 produced the true tree in all tree-building methods or
algorithms for both amino acid and nucleotide sequence data. Genes Cytb and
Nd4 also produced the correct tree in most tree-building algorithms when
amino acid sequence data were used. By contrast, Co2, Nd1, and Nd41 showed
a poor performance. In general, large genes produced better results, and
when the entire set of genes was used, all tree-building methods generated
the true tree. In each tree-building method, several distance measures or
algorithms were used, but all these distance measures or algorithms
produced essentially the same results. The ME method, in which many
different topologies are examined, was no better than the NJ method, which
generates a single final tree. Similarly, an ML method, in which many
topologies are examined, was no better than the ML star decomposition
algorithm that generates a single final tree. In ML the best substitution
model chosen by using the Akaike information criterion produced no better
results than simpler substitution models. These results question the
utility of the currently used optimization principles in phylogenetic
construction. Relatively simple methods such as the NJ and ML star
decomposition algorithms seem to produce as good results as those obtained
by more sophisticated methods. The efficiencies of the NJ, ME, MP, and ML
methods in obtaining the correct tree were nearly the same when amino acid
sequence data were used. The most important factor in constructing reliable
phylogenetic trees seems to be the number of amino acids or nucleotides
used.
相似文献
48.
Interaction of L- and D-3-amino-1-chloro-2-pentanone with gamma-glutamylcysteine synthetase 总被引:1,自引:0,他引:1
R L Beamer O W Griffith J D Gass M E Anderson A Meister 《The Journal of biological chemistry》1980,255(24):11732-11736
The optical isomers of 3-amino-1-chloro-2-pentanone, which are the alpha-chloroketone analogs of L- and D-alpha-aminobutyrate, were synthesized and found to be highly potent irreversible inactivators of gamma-glutamylcysteine synthetase. These chloroketones are 20 to 30 times more active than L-2-amino-4-oxo-5-chlorpentanoate. L- and D-Glutamate, in the presence of Mg2+ or Mn2+, protect the enzyme against inactivation. The enzyme is almost completely inhibited by cystamine under conditions in which 0.5 mol of this compound is bound/mol of enzyme. Treatment of the enzyme with cystamne, which produces inhibition that is reversible by dithiothreitol, prevents the interaction of the new chloroketones, L-2-amino-4-oxo-5-chloropentanoate and methionine sulfoximine with the enzyme. The findings suggest that a sulfhydryl group at the active site interacts with the chloroketones and with cystamine and that the chloroketone inhibitors and cystamine bind to the enzyme as glutamine analogs. The data also suggest that a gamma-glutamyl-S-enzyme intermediate may be formed in the reaction catalyzed by this enzyme. 相似文献
49.
Ilse Hurbain-Kosmath Annette Berault Nadine Noel Jolanta Polkowska Anne Bohin Marian Jutisz Edward H. Leiter Wesley G. Beamer Hendrick G. Bedigian Muriel T. Davisson David E. Harrison 《In vitro cellular & developmental biology. Plant》1990,26(5):431-440
Summary An epithelial cell line (RC-4B/C) was established from a pituitary adenoma obtained from a 3-yr-old (ACI/fMai × F344/fMai)F1
male rat. Before Year 5 in vitro, RC-4B/C cells could not be viably recovered from cryogenic storage. Recovery of viable cells
from cryogenic storage in Year 5 was associated with a more transformed phenotype, including the appearance of endogenous
C-type rat retroviral particles. The ultrastructural appearance of the cells was similar to that of differentiated anterior
pituitary cell; the cultured cells contained numerous, electron dense, secretory granules, Golgi complexes, and extended arrays
of rough endoplasmic reticulum. Immunocytochemical study showed that all cell types present in the rat anterior pituitary
gland were present in the cell line. The percentage of luteinizing hormone beta (LHβ) cells in the cell line was higher (19.9%)
and that of growth hormone cells was lower (12.2%) than in normal male rat pituitary, whereas the cell line contained a comparable
percentage of follicle stimulating hormone beta (FSHβ), prolactin (PRL), ACTH, and thyrotropin beta cells. Radioimmunoassay
data demonstrated the PRL content of the cells was comparable to that of normal male rat pituitary gland, whereas the content
of LH and FSH was 70- and 800-fold lower, respectively. Assay of specific receptor sites for gonadotropin releasing hormone
(GnRH) using Scatchard plots of the data established the RC-4B/C cells contained GnRH receptor sites of the same affinity
as in the pituitary gland, but of twofold lower capacity. These data suggest the RC-4B/C cell line warrants further study
as a model for the induction and maintenance of the gonadotropic function of the pituitary gland.
An abstract of portions of these results was presented at the 8th International Congress of Endocrinology, Kyoto, Japan, 1988.
This work was supported in part by grants DK-17631 (E.H.L.), CA-24145 (W.G.B.), CA-31102 (H.G.B.), AG-01753 (D.E.H.) and HD-1778
(M.T.D.) from the National Institutes of Health, Bethesda, MD, and by a grant from the Association pour la Recherche sur le
Cancer, France (M.J.). The NIH is not responsible for the contents of this publication nor do the contents necessarily represent
the official views of that agency.
Jolanta Polkowska was a recipient of a Foundation Simone et Cino del Duca grant. 相似文献
50.
Emily K. LuebberingJacob Mick Ranjan K. SinghJohn J. Tanner Ritcha Mehra-ChaudharyLesa J. Beamer 《Journal of molecular biology》2012,423(5):831-846
The α‐d‐phosphohexomutase superfamily comprises enzymes involved in carbohydrate metabolism that are found in all kingdoms of life. Recent biophysical studies have shown for the first time that several of these enzymes exist as dimers in solution, prompting an examination of the oligomeric state of all proteins of known structure in the superfamily (11 different proteins; 31 crystal structures) via computational and experimental analyses. We find that these proteins range in quaternary structure from monomers to tetramers, with 6 of the 11 known structures being likely oligomers. The oligomeric state of these proteins not only is associated in some cases with enzyme subgroup (i.e., substrate specificity) but also appears to depend on domain of life, with the two archaeal proteins existing as higher‐order oligomers. Within the oligomers, three distinct interfaces are observed, one of which is found in both archaeal and bacterial proteins. Normal mode analysis shows that the topological arrangement of the oligomers permits domain 4 of each protomer to move independently as required for catalysis. Our analysis suggests that the advantages associated with protein flexibility in this enzyme family are of sufficient importance to be maintained during the evolution of multiple independent oligomers. This study is one of the first showing that global motions may be conserved not only within protein families but also across members of a superfamily with varying oligomeric structures. 相似文献