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51.
SCRAPPER-dependent ubiquitination of active zone protein RIM1 regulates synaptic vesicle release 总被引:1,自引:0,他引:1
Yao I Takagi H Ageta H Kahyo T Sato S Hatanaka K Fukuda Y Chiba T Morone N Yuasa S Inokuchi K Ohtsuka T Macgregor GR Tanaka K Setou M 《Cell》2007,130(5):943-957
Little is known about how synaptic activity is modulated in the central nervous system. We have identified SCRAPPER, a synapse-localized E3 ubiquitin ligase, which regulates neural transmission. SCRAPPER directly binds and ubiquitinates RIM1, a modulator of presynaptic plasticity. In neurons from Scrapper-knockout (SCR-KO) mice, RIM1 had a longer half-life with significant reduction in ubiquitination, indicating that SCRAPPER is the predominant ubiquitin ligase that mediates RIM1 degradation. As anticipated in a RIM1 degradation defect mutant, SCR-KO mice displayed altered electrophysiological synaptic activity, i.e., increased frequency of miniature excitatory postsynaptic currents. This phenotype of SCR-KO mice was phenocopied by RIM1 overexpression and could be rescued by re-expression of SCRAPPER or knockdown of RIM1. The acute effects of proteasome inhibitors, such as upregulation of RIM1 and the release probability, were blocked by the impairment of SCRAPPER. Thus, SCRAPPER has an essential function in regulating proteasome-mediated degradation of RIM1 required for synaptic tuning. 相似文献
52.
Sequential aldol condensation catalyzed by hyperthermophilic 2-deoxy-d-ribose-5-phosphate aldolase 总被引:1,自引:0,他引:1
Sakuraba H Yoneda K Yoshihara K Satoh K Kawakami R Uto Y Tsuge H Takahashi K Hori H Ohshima T 《Applied and environmental microbiology》2007,73(22):7427-7434
Genes encoding 2-deoxy-d-ribose-5-phosphate aldolase (DERA) homologues from two hyperthermophiles, the archaeon Pyrobaculum aerophilum and the bacterium Thermotoga maritima, were expressed individually in Escherichia coli, after which the structures and activities of the enzymes produced were characterized and compared with those of E. coli DERA. To our surprise, the two hyperthermophilic DERAs showed much greater catalysis of sequential aldol condensation using three acetaldehydes as substrates than the E. coli enzyme, even at a low temperature (25 degrees C), although both enzymes showed much less 2-deoxy-d-ribose-5-phosphate synthetic activity. Both the enzymes were highly resistant to high concentrations of acetaldehyde and retained about 50% of their initial activities after a 20-h exposure to 300 mM acetaldehyde at 25 degrees C, whereas the E. coli DERA was almost completely inactivated after a 2-h exposure under the same conditions. The structure of the P. aerophilum DERA was determined by X-ray crystallography to a resolution of 2.0 A. The main chain coordinate of the P. aerophilum enzyme monomer was quite similar to those of the T. maritima and E. coli enzymes, whose crystal structures have already been solved. However, the quaternary structure of the hyperthermophilic enzymes was totally different from that of the E. coli DERA. The areas of the subunit-subunit interface in the dimer of the hyperthermophilic enzymes are much larger than that of the E. coli enzyme. This promotes the formation of the unique dimeric structure and strengthens the hydrophobic intersubunit interactions. These structural features are considered responsible for the extremely high stability of the hyperthermophilic DERAs. 相似文献
53.
Comparative metagenomics revealed commonly enriched gene sets in human gut microbiomes. 总被引:10,自引:1,他引:9
Ken Kurokawa Takehiko Itoh Tomomi Kuwahara Kenshiro Oshima Hidehiro Toh Atsushi Toyoda Hideto Takami Hidetoshi Morita Vineet K Sharma Tulika P Srivastava Todd D Taylor Hideki Noguchi Hiroshi Mori Yoshitoshi Ogura Dusko S Ehrlich Kikuji Itoh Toshihisa Takagi Yoshiyuki Sakaki Tetsuya Hayashi Masahira Hattori 《DNA research》2007,14(4):169-181
Numerous microbes inhabit the human intestine, many of which are uncharacterized or uncultivable. They form a complex microbial community that deeply affects human physiology. To identify the genomic features common to all human gut microbiomes as well as those variable among them, we performed a large-scale comparative metagenomic analysis of fecal samples from 13 healthy individuals of various ages, including unweaned infants. We found that, while the gut microbiota from unweaned infants were simple and showed a high inter-individual variation in taxonomic and gene composition, those from adults and weaned children were more complex but showed a high functional uniformity regardless of age or sex. In searching for the genes over-represented in gut microbiomes, we identified 237 gene families commonly enriched in adult-type and 136 families in infant-type microbiomes, with a small overlap. An analysis of their predicted functions revealed various strategies employed by each type of microbiota to adapt to its intestinal environment, suggesting that these gene sets encode the core functions of adult and infant-type gut microbiota. By analysing the orphan genes, 647 new gene families were identified to be exclusively present in human intestinal microbiomes. In addition, we discovered a conjugative transposon family explosively amplified in human gut microbiomes, which strongly suggests that the intestine is a 'hot spot' for horizontal gene transfer between microbes. 相似文献
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56.
Shota Sawake Noriaki Tajima Jenny C. Mortimer Jeemeng Lao Toshiki Ishikawa Xiaolan Yu Yukiko Yamanashi Yoshihisa Yoshimi Maki Kawai-Yamada Paul Dupree Yoichi Tsumuraya Toshihisa Kotake 《The Plant cell》2015,27(12):3397-3409
Humans are unable to synthesize l-ascorbic acid (AsA), yet it is required as a cofactor in many critical biochemical reactions. The majority of human dietary AsA is obtained from plants. In Arabidopsis thaliana, a GDP-mannose pyrophosphorylase (GMPP), VITAMIN C DEFECTIVE1 (VTC1), catalyzes a rate-limiting step in AsA synthesis: the formation of GDP-Man. In this study, we identified two nucleotide sugar pyrophosphorylase-like proteins, KONJAC1 (KJC1) and KJC2, which stimulate the activity of VTC1. The kjc1kjc2 double mutant exhibited severe dwarfism, indicating that KJC proteins are important for growth and development. The kjc1 mutation reduced GMPP activity to 10% of wild-type levels, leading to a 60% reduction in AsA levels. On the contrary, overexpression of KJC1 significantly increased GMPP activity. The kjc1 and kjc1kjc2 mutants also exhibited significantly reduced levels of glucomannan, which is also synthesized from GDP-Man. Recombinant KJC1 and KJC2 enhanced the GMPP activity of recombinant VTC1 in vitro, while KJCs did not show GMPP activity. Yeast two-hybrid assays suggested that the stimulation of GMPP activity occurs via interaction of KJCs with VTC1. These results suggest that KJCs are key factors for the generation of GDP-Man and affect AsA level and glucomannan accumulation through the stimulation of VTC1 GMPP activity. 相似文献
57.
Chonan T Wakasugi D Yamamoto D Yashiro M Oi T Tanaka H Ohoka-Sugita A Io F Koretsune H Hiratate A 《Bioorganic & medicinal chemistry》2011,19(5):1580-1593
Novel (4-piperidinyl)-piperazine derivatives were synthesized and evaluated as ACC1/2 non-selective inhibitors. Optimization of the substituents on the nitrogen of the piperidine ring led to the identification of the fluorine substituted tert-butoxycarbonyl group. Advanced analog, 1,1,1-trifluoro-2-methylpropan-2-yl 4-{4-[(2-amino-6-methyl-1-benzothiophen-3-yl)carbonyl]piperazin-1-yl}piperidine-1-carboxylate (12c) showed potent inhibitory activities in enzyme-assay and cell-based assays. Compound 12c also exhibited reduction of hepatic de novo fatty acid synthesis in rats after oral administration. 相似文献
58.
The temperature‐dependent photoluminescences of Y2O3:Eu (6% Eu), Y2O3:Tb (4% Tb) and Y2O3:Tm (1% Tm) were investigated for high‐temperature phosphor thermometry. Two different phases, the monoclinic phase and cubic phase, were considered because the fluorescence spectra vary with the phase. To employ the intensity ratio method, we investigated their photoluminescence spectra under the excitation light of an Hg–Xe lamp as the temperature was elevated from room temperature to more than 1200 K. As a result, it was confirmed that the luminescence intensity of all of the phosphors varied with elevating temperature, i.e. thermal quenching, with the variations depending on the type of rare earth impurity and their phases. The results indicate that Y2O3:Eu phosphors are applicable to the intensity ratio method because they show appropriate variations in the intensity ratio of two emission lines, and they also have strong and sharp peak intensities without excessive optical noise or black body radiation over a wide range of temperatures. The intensity ratios for Y2O3:Tb provide such small variations with temperature that the temperature resolution is low, despite the strong emission intensities. As for Y2O3:Tm, the intensity ratios also have a low temperature resolution and their emission intensities are weak. Therefore, Y2O3:Tb and Y2O3:Tm are not appropriate for the intensity ratio method for phosphor thermometry. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
59.
Aims: Bacterial communities in the apple phyllosphere were examined quantitatively and qualitatively by applying culture‐dependent and culture‐independent methods. Methods and Results: Populations estimated by viewing cells stained with 4′,6‐diamidino‐2‐phenylindole generally were at least 100–1000 times greater than populations estimated by culturing on tryptic soy agar (TSA). Of the 44 operational taxonomic units (OTUs; cut‐off threshold of 97%) detected in total, five bacterial orders containing 23 OTUs were identified by culturing on TSA, whereas nine orders containing 33 OTUs were identified by 16S rRNA gene cloning of DNA extracted from apple leaf surfaces. Twelve of the 44 OTUs were shared between cultured isolates and 16S rRNA gene clones and included the orders Burkholderiales, Pseudomonadales, Rhizobiales and Sphingomonadales. Three OTUs within the genus Sphingomonas accounted for 40% of isolates and 68% of clones. The Actinomycetales were found only among isolates, whereas the Bacteroidales, Enterobacteriales, Myxococales and Sphingobacteriales were represented in the 16S rRNA gene clone libraries but were absent among isolates. Conclusions: Culture‐independent methods revealed greater numbers and greater richness of bacteria on apple leaves than found by culturing. Significance and Impact of the Study: This is the first study to directly compare culture‐dependent and independent approaches for assessing bacterial communities in the phyllosphere. The biases introduced by different methods will have a significant impact on studies related to phyllosphere ecology, biological control of plant diseases, reservoirs of antibiotic resistance genes and food safety. 相似文献
60.
Yamauchi Y Izumi Y Kawamura M Nakatsuka S Yashiro H Tsukada N Inoue M Asakura K Nomori H 《PloS one》2011,6(11):e27086