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排序方式: 共有65条查询结果,搜索用时 343 毫秒
21.
选用C57BL/6小鼠,随机分为两组.实验组小鼠通过匹罗卡品(PILO)腹腔注射,诱发癫痫持续状态(SE);对照组给予等容量生理盐水.SE后4周测试小鼠听力,SE后6~7周播放莫扎特K.448,探究莫扎特K.448对颞叶癫痫模型鼠自发发作期高频脑电(EEG)活性的影响.数据显示,PILO注射未明显影响小鼠的听力,给予莫扎特K.448使对照组与SE模型鼠在55~145 Hz区间的功率谱显著升高.结果表明,短时期给予莫扎特K.448音乐治疗能导致小鼠EEG高频活性增强. 相似文献
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King N Westbrook MJ Young SL Kuo A Abedin M Chapman J Fairclough S Hellsten U Isogai Y Letunic I Marr M Pincus D Putnam N Rokas A Wright KJ Zuzow R Dirks W Good M Goodstein D Lemons D Li W Lyons JB Morris A Nichols S Richter DJ Salamov A Sequencing JG Bork P Lim WA Manning G Miller WT McGinnis W Shapiro H Tjian R Grigoriev IV Rokhsar D 《Nature》2008,451(7180):783-788
Choanoflagellates are the closest known relatives of metazoans. To discover potential molecular mechanisms underlying the evolution of metazoan multicellularity, we sequenced and analysed the genome of the unicellular choanoflagellate Monosiga brevicollis. The genome contains approximately 9,200 intron-rich genes, including a number that encode cell adhesion and signalling protein domains that are otherwise restricted to metazoans. Here we show that the physical linkages among protein domains often differ between M. brevicollis and metazoans, suggesting that abundant domain shuffling followed the separation of the choanoflagellate and metazoan lineages. The completion of the M. brevicollis genome allows us to reconstruct with increasing resolution the genomic changes that accompanied the origin of metazoans. 相似文献
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Zhang J Benavente CA McEvoy J Flores-Otero J Ding L Chen X Ulyanov A Wu G Wilson M Wang J Brennan R Rusch M Manning AL Ma J Easton J Shurtleff S Mullighan C Pounds S Mukatira S Gupta P Neale G Zhao D Lu C Fulton RS Fulton LL Hong X Dooling DJ Ochoa K Naeve C Dyson NJ Mardis ER Bahrami A Ellison D Wilson RK Downing JR Dyer MA 《Nature》2012,481(7381):329-334
Retinoblastoma is an aggressive childhood cancer of the developing retina that is initiated by the biallelic loss of RB1. Tumours progress very quickly following RB1 inactivation but the underlying mechanism is not known. Here we show that the retinoblastoma genome is stable, but that multiple cancer pathways can be epigenetically deregulated. To identify the mutations that cooperate with RB1 loss, we performed whole-genome sequencing of retinoblastomas. The overall mutational rate was very low; RB1 was the only known cancer gene mutated. We then evaluated the role of RB1 in genome stability and considered non-genetic mechanisms of cancer pathway deregulation. For example, the proto-oncogene SYK is upregulated in retinoblastoma and is required for tumour cell survival. Targeting SYK with a small-molecule inhibitor induced retinoblastoma tumour cell death in vitro and in vivo. Thus, retinoblastomas may develop quickly as a result of the epigenetic deregulation of key cancer pathways as a direct or indirect result of RB1 loss. 相似文献
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Evolution of the chalcone-isomerase fold from fatty-acid binding to stereospecific catalysis 总被引:1,自引:0,他引:1
Ngaki MN Louie GV Philippe RN Manning G Pojer F Bowman ME Li L Larsen E Wurtele ES Noel JP 《Nature》2012,485(7399):530-533
Specialized metabolic enzymes biosynthesize chemicals of ecological importance, often sharing a pedigree with primary metabolic enzymes. However, the lineage of the enzyme chalcone isomerase (CHI) remained unknown. In vascular plants, CHI-catalysed conversion of chalcones to chiral (S)-flavanones is a committed step in the production of plant flavonoids, compounds that contribute to attraction, defence and development. CHI operates near the diffusion limit with stereospecific control. Although associated primarily with plants, the CHI fold occurs in several other eukaryotic lineages and in some bacteria. Here we report crystal structures, ligand-binding properties and in vivo functional characterization of a non-catalytic CHI-fold family from plants. Arabidopsis thaliana contains five actively transcribed genes encoding CHI-fold proteins, three of which additionally encode amino-terminal chloroplast-transit sequences. These three CHI-fold proteins localize to plastids, the site of de novo fatty-acid biosynthesis in plant cells. Furthermore, their expression profiles correlate with those of core fatty-acid biosynthetic enzymes, with maximal expression occurring in seeds and coinciding with increased fatty-acid storage in the developing embryo. In vitro, these proteins are fatty-acid-binding proteins (FAPs). FAP knockout A. thaliana plants show elevated α-linolenic acid levels and marked reproductive defects, including aberrant seed formation. Notably, the FAP discovery defines the adaptive evolution of a stereospecific and catalytically 'perfected' enzyme from a non-enzymatic ancestor over a defined period of plant evolution. 相似文献
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Manning AK Hivert MF Scott RA Grimsby JL Bouatia-Naji N Chen H Rybin D Liu CT Bielak LF Prokopenko I Amin N Barnes D Cadby G Hottenga JJ Ingelsson E Jackson AU Johnson T Kanoni S Ladenvall C Lagou V Lahti J Lecoeur C Liu Y Martinez-Larrad MT Montasser ME Navarro P Perry JR Rasmussen-Torvik LJ Salo P Sattar N Shungin D Strawbridge RJ Tanaka T van Duijn CM An P de Andrade M Andrews JS Aspelund T Atalay M Aulchenko Y Balkau B Bandinelli S Beckmann JS Beilby JP Bellis C Bergman RN Blangero J 《Nature genetics》2012,44(6):659-669
Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology. 相似文献
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Substitution of arginine for glutamine in the 4-position of a vasopressin V1 antagonist has been reported to turn it into an agonist. We resynthesized this 4-arginine analog and synthesized additional cyclic and linear vasopressin antagonists containing a 4-arginine. The presence of a 4-arginine in the resynthesized and new analogs had relatively minor effects on their antivasopressin V1 and V2 antagonistic potencies. 相似文献
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