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排序方式: 共有153条查询结果,搜索用时 15 毫秒
1.
Many molecules can rotate freely around single bonds and thereby interconvert between different conformations, such as gauche and anti 1,2-disubstituted ethane, a classic example of conformational isomerism. Even though rotation occurs rapidly at room temperature, the product selectivity seen in some reactions has been explained by conformation-dependent reaction mechanisms: if reactant molecules differing only in their conformation are located at different positions on the reaction path, they may undergo different reactions. But a direct verification of this effect is difficult, because the energy barrier separating conformational isomers is so low that under ambient conditions reactants with more than one conformation will be present. But by using temperatures low enough to suppress the interconversion between different conformations, gauche-1-iodopropane ions and anti-1-iodopropane ions have been selectively generated. Here we show that the kinetic energy released during the photodissociation of 1-iodopropane ions depends strongly on the conformation of the ions. Thermodynamic arguments and ab initio calculations indicate that this difference in kinetic energy release results from differences in the reaction mechanism, with gauche-1-iodopropane ions forming 2-propyl ions and anti-1-iodopropane ions forming protonated cyclopropane ions. These findings suggest that the well-known concept of conformation selection forms the basis of a simple scheme for reaction control, thus providing in some cases an attractive alternative for more involved schemes that utilize the phase and pulse shape of laser beams to control chemical reactions. 相似文献
2.
从1995年开始实行的韩国质量革新计划(SinglePPM)运动是为了提高从合作企业纳入的产品质量。此项运动的目标是将包括成品不合格率和区域索赔的交货不合格率减少至10ppm以内或100ppm以下。至今,从韩国政府获得S-PPM认证的企业有1053家。这项质量革新计划不单纯是为提高产品质量,而且也为提高企业的信誉度做贡献。 相似文献
3.
Tae-In Kam Youngdae Gwon Yong-Keun Jung 《Cellular and molecular life sciences : CMLS》2014,71(24):4803-4813
Alzheimer’s disease (AD) is the most common neurodegenerative disease. Although a major cause of AD is the accumulation of amyloid-β (Aβ) peptide that induces neuronal loss and cognitive impairments, our understanding of its neurotoxic mechanisms is limited. Recent studies have identified putative Aβ-binding receptors that mediate Aβ neurotoxicity in cells and models of AD. Once Aβ interacts with a receptor, a toxic signal is transduced into neurons, resulting in cellular defects including endoplasmic reticulum stress and mitochondrial dysfunction. In addition, Aβ can also be internalized into neurons through unidentified Aβ receptors and induces malfunction of subcellular organelles, which explains some part of Aβ neurotoxicity. Understanding the neurotoxic signaling initiated by Aβ-receptor binding and cellular defects provide insight into new therapeutic windows for AD. In the present review, we summarize the findings on Aβ-binding receptors and the neurotoxicity of oligomeric Aβ. 相似文献
4.
Jinwon Lim Hyo-Jung Lee Bonglee Kim Jeong-Un Choi Yoeok Shin Eun Jung Sohn Sung-Hoon Kim 《科学通报(英文版)》2014,59(25):3127-3133
Though Hongbaekjeong(HBJ),a hebal mixture of three medicinal plants,has been traditionally used for arthritis and muscular pain,its scientific evidence still remains unclear.Thus,in the present study,analgesic and anti-inflammatory mechanism of HBJ was evaluated in vitro and in vivo.HBJ significantly reduced NO production and prostaglandin E2(PGE2)release and also attenuated the expression of cyclooxygenase 2(COX-2)in lipopolysaccharides(LPS)and interferon(IFN)-c treated RAW 264.7 cells.Furthermore,HBJ abrogated the production of proinflammatory cytokines such as interleukin(IL)1b,IL-6,IL-8 and monocyte chemoattractant protein-1(MCP-1)in LPS and IFN-c treated RAW 264.7 cells.In addition,HBJ significantly decreased the number of writhing syndrome induced by acetic acid,and also increased latency in hot-plate method and tail flick test in mice.Consistently,HBJ significantly reduced the edema volume in the hind paw of the rats with arthritis induced by Freund’s complete adjuvant(FCA)compared to untreated control.Collectively,our findings demonstrate the antiinflammatory and analgesic potential of HBJ via inhibition of proinflammatory cytokines and PGE2 release for treatment of arthritis and muscular pain. 相似文献
5.
Kharchenko PV Alekseyenko AA Schwartz YB Minoda A Riddle NC Ernst J Sabo PJ Larschan E Gorchakov AA Gu T Linder-Basso D Plachetka A Shanower G Tolstorukov MY Luquette LJ Xi R Jung YL Park RW Bishop EP Canfield TK Sandstrom R Thurman RE MacAlpine DM Stamatoyannopoulos JA Kellis M Elgin SC Kuroda MI Pirrotta V Karpen GH Park PJ 《Nature》2011,471(7339):480-485
Chromatin is composed of DNA and a variety of modified histones and non-histone proteins, which have an impact on cell differentiation, gene regulation and other key cellular processes. Here we present a genome-wide chromatin landscape for Drosophila melanogaster based on eighteen histone modifications, summarized by nine prevalent combinatorial patterns. Integrative analysis with other data (non-histone chromatin proteins, DNase I hypersensitivity, GRO-Seq reads produced by engaged polymerase, short/long RNA products) reveals discrete characteristics of chromosomes, genes, regulatory elements and other functional domains. We find that active genes display distinct chromatin signatures that are correlated with disparate gene lengths, exon patterns, regulatory functions and genomic contexts. We also demonstrate a diversity of signatures among Polycomb targets that include a subset with paused polymerase. This systematic profiling and integrative analysis of chromatin signatures provides insights into how genomic elements are regulated, and will serve as a resource for future experimental investigations of genome structure and function. 相似文献
6.
Kaneko H Dridi S Tarallo V Gelfand BD Fowler BJ Cho WG Kleinman ME Ponicsan SL Hauswirth WW Chiodo VA Karikó K Yoo JW Lee DK Hadziahmetovic M Song Y Misra S Chaudhuri G Buaas FW Braun RE Hinton DR Zhang Q Grossniklaus HE Provis JM Madigan MC Milam AH Justice NL Albuquerque RJ Blandford AD Bogdanovich S Hirano Y Witta J Fuchs E Littman DR Ambati BK Rudin CM Chong MM Provost P Kugel JF Goodrich JA Dunaief JL Baffi JZ Ambati J 《Nature》2011,471(7338):325-330
7.
Shimamura T Shiroishi M Weyand S Tsujimoto H Winter G Katritch V Abagyan R Cherezov V Liu W Han GW Kobayashi T Stevens RC Iwata S 《Nature》2011,475(7354):65-70
The biogenic amine histamine is an important pharmacological mediator involved in pathophysiological processes such as allergies and inflammations. Histamine H(1) receptor (H(1)R) antagonists are very effective drugs alleviating the symptoms of allergic reactions. Here we show the crystal structure of the H(1)R complex with doxepin, a first-generation H(1)R antagonist. Doxepin sits deep in the ligand-binding pocket and directly interacts with Trp?428(6.48), a highly conserved key residue in G-protein-coupled-receptor activation. This well-conserved pocket with mostly hydrophobic nature contributes to the low selectivity of the first-generation compounds. The pocket is associated with an anion-binding region occupied by a phosphate ion. Docking of various second-generation H(1)R antagonists reveals that the unique carboxyl group present in this class of compounds interacts with Lys?191(5.39) and/or Lys?179(ECL2), both of which form part of the anion-binding region. This region is not conserved in other aminergic receptors, demonstrating how minor differences in receptors lead to pronounced selectivity differences with small molecules. Our study sheds light on the molecular basis of H(1)R antagonist specificity against H(1)R. 相似文献
8.
Spatio-temporal transcriptome of the human brain 总被引:1,自引:0,他引:1
9.
Gout AM;ADPKD Gene Variant Consortium Ravine D Harris PC Rossetti S Peters D Breuning M Henske EP Koizumi A Inoue S Shimizu Y Thongnoppakhun W Yenchitsomanus PT Deltas C Sandford R Torra R Turco AE Jeffery S Fontes M Somlo S Furu LM Smulders YM Mercier B Ferec C Burtey S Pei Y Kalaydjieva L Bogdanova N McCluskey M Geon LJ Wouters CH Reiterova J Stekrová J San Millan JL Aguiari G Del Senno L 《Nature genetics》2007,39(4):427-428
10.
Lena Golick Youngah Han Yoo Kim Sang Won Park 《Cellular and molecular life sciences : CMLS》2018,75(10):1857-1869
Reduced hepatic expression levels of bromodomain-containing protein 7 (BRD7) have been suggested to play a role in the development of glucose intolerance in obesity. However, the molecular mechanism by which BRD7 regulates glucose metabolism has remained unclear. Here, we show that BRD7 increases phosphorylation of glycogen synthase kinase 3β (GSK3β) in response to activation of the insulin receptor-signaling pathway shortly after insulin stimulation and the nutrient-sensing pathway after feeding. BRD7 mediates phosphorylation of GSK3β at the Serine 9 residue and this effect on GSK3β occurs even in the absence of AKT activity. Using both in vitro and in vivo models, we further demonstrate that BRD7 mediates phosphorylation of ribosomal protein S6 kinase (S6K) and leads to increased phosphorylation of the eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and, therefore, relieves its inhibition of the eukaryotic translation initiation factor 4E (eIF4E). However, the increase in phosphorylation of 4E-BP1 with BRD7 overexpression is blunted in the absence of AKT activity. In addition, using liver-specific BRD7 knockout (LBKO) mice, we show that BRD7 is required for mTORC1 activity on its downstream molecules. These findings show a novel basis for understanding the molecular dynamics of glucose metabolism and suggest the unique function of BRD7 in the regulation of glucose homeostasis. 相似文献