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排序方式: 共有156条查询结果,搜索用时 31 毫秒
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Seetharamaiyer Padmanabhan Ruth C. Lavin Paresh M. Thakker Jinqing Guo Lu Zhang Deke Moore Michael E. Perlman Cassandra Kirk Deborah Daly Kathy J. Burke-Howie Teresa Wolcott Suchitra Chari David Berlove James B. Fischer William F. Holt Graham J. Durant Robert N. McBurney 《Bioorganic & medicinal chemistry letters》2001,11(24):1945-3155
Solution-phase synthesis of various acylguanidine derivatives and the evaluation of a small library of compounds as potential sodium channel blockers are described. 相似文献
23.
Twenty-five dogs were exposed to gradual coronary occlusion by placing Ameroid constrictors around the origins of the left circumflex and anterior descending coronary arteries. Previous experiments have demonstrated that these constrictors absorb water and, over a period of three weeks, narrow the cross-sectional area of the two arteries to 50% or less, and consequently cause the death of 80% of the experimental animals. Twelve of the 25 animals were fed 50 mg. of Persantin three times a day by mouth commencing one day before the operative procedure. Determinations of the concentration of the drug in the blood revealed a level consistent with that obtained in humans after the administration of therapeutic doses. Eleven of the 13 control animals died in the three-month experimental period while only six of the 12 treated animals expired. Injections of Schlesinger mass in all animals dying or killed following the experimental period demonstrated that Persantin significantly accelerated the development of intercoronary anastomoses in the treated group, and in the surviving animals produced a rich anastomotic network much in excess of that seen in the surviving animals in the control series that were exposed to hypoxia alone. On the basis of these experimental findings, it is suggested that Persantin may favourably alter the prognosis of many patients with coronary artery disease. 相似文献
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Link AJ Skretas G Strauch EM Chari NS Georgiou G 《Protein science : a publication of the Protein Society》2008,17(10):1857-1863
G protein-coupled receptors (GPCRs) are notoriously difficult to express, particularly in microbial systems. Using GPCR fusions with the green fluorescent protein (GFP), we conducted studies to identify bacterial host effector genes that result in a general and significant enhancement in the amount of membrane-integrated human GPCRs that can be produced in Escherichia coli. We show that coexpression of the membrane-bound AAA+ protease FtsH greatly enhances the expression yield of four different class I GPCRs, irrespective of the presence of GFP. Using this new expression system, we produced 0.5 and 2 mg/L of detergent-solubilized and purified full-length central cannabinoid receptor (CB1) and bradykinin receptor 2 (BR2) in shake flask cultures, respectively, two proteins that had previously eluded expression in microbial systems. 相似文献
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Rui Pedro Gal?o Ashwin Chari Isabel Alves-Rodrigues Daniela Lob?o Antonio Mas Christian Kambach Utz Fischer Juana Díez 《RNA (New York, N.Y.)》2010,16(4):817-827
LSm1-7 complexes promote cellular mRNA degradation, in addition to translation and replication of positive-strand RNA viruses such as the Brome mosaic virus (BMV). Yet, how LSm1-7 complexes act on their targets remains elusive. Here, we report that reconstituted recombinant LSm1-7 complexes directly bind to two distinct RNA-target sequences in the BMV genome, a tRNA-like structure at the 3′-untranslated region and two internal A-rich single-stranded regions. Importantly, in vivo analysis shows that these sequences regulate the translation and replication of the BMV genome. Furthermore, both RNA-target sequences resemble those found for Hfq, the LSm counterpart in bacteria, suggesting conservation through evolution. Our results provide the first evidence that LSm1-7 complexes interact directly with viral RNA genomes and open new perspectives in the understanding of LSm1-7 functions. 相似文献
28.
Georges Martin Antje Ostareck-Lederer Ashwin Chari Nils Neuenkirchen Sabine Dettwiler Diana Blank Ursula Rüegsegger Utz Fischer Walter Keller 《RNA (New York, N.Y.)》2010,16(8):1646-1659
Mammalian cleavage factor I (CF Im) is composed of two polypeptides of 25 kDa and either a 59 or 68 kDa subunit (CF Im25, CF Im59, CF Im68). It is part of the cleavage and polyadenylation complex responsible for processing the 3′ ends of messenger RNA precursors. To investigate post-translational modifications in factors of the 3′ processing complex, we systematically searched for enzymes that modify arginines by the addition of methyl groups. Protein arginine methyltransferases (PRMTs) are such enzymes that transfer methyl groups from S-adenosyl methionine to arginine residues within polypeptide chains resulting in mono- or dimethylated arginines. We found that CF Im68 and the nuclear poly(A) binding protein 1 (PABPN1) were methylated by HeLa cell extracts in vitro. By fractionation of these extracts followed by mass spectral analysis, we could demonstrate that the catalytic subunit PRMT5, together with its cofactor WD45, could symmetrically dimethylate CF Im68, whereas pICln, the third polypeptide of the complex, was stimulatory. As sites of methylation in CF Im68 we could exclusively identify arginines in a GGRGRGRF or “GAR” motif that is conserved in vertebrates. Further in vitro assays revealed a second methyltransferase, PRMT1, which modifies CF Im68 by asymmetric dimethylation of the GAR motif and also weakly methylates the C-termini of both CF Im59 and CF Im68. The results suggest that native—as compared with recombinant—protein substrates may contain additional determinants for methylation by specific PRMTs. A possible involvement of CF Im methylation in the context of RNA export is discussed. 相似文献
29.
Mai Xu Lindsey Mehl Tongwu Zhang Rohit Thakur Hayley Sowards Timothy Myers Lea Jessop Alessandra Chesi Matthew E. Johnson Andrew D. Wells Helen T. Michael Patricia Bunda Kristine Jones Herbert Higson Rebecca C. Hennessey Ashley Jermusyk Michael A. Kovacs Maria Teresa Landi Mark M. Iles Alisa M. Goldstein Melanoma Meta-Analysis Consortium Jiyeon Choi Stephen J. Chanock Struan F.A. Grant Raj Chari Glenn Merlino Matthew H. Law Kevin M. Brown 《American journal of human genetics》2021,108(9):1611-1630
30.
The mitochondrial tyrosyl-tRNA synthetases (mt TyrRSs) of Pezizomycotina fungi are bifunctional proteins that aminoacylate mitochondrial tRNA(Tyr) and are structure-stabilizing splicing cofactors for group I introns. Studies with the Neurospora crassa synthetase (CYT-18 protein) showed that splicing activity is dependent upon Pezizomycotina-specific structural adaptations that form a distinct group I intron-binding site in the N-terminal catalytic domain. Although CYT-18's C-terminal domain also binds group I introns, it has been intractable to X-ray crystallography in the full-length protein. Here, we determined an NMR structure of the isolated C-terminal domain of the Aspergillus nidulans mt TyrRS, which is closely related to but smaller than CYT-18's. The structure shows an S4 fold like that of bacterial TyrRSs, but with novel features, including three Pezizomycontia-specific insertions. (15)N-(1)H two-dimensional NMR showed that C-terminal domains of the full-length A. nidulans and Geobacillus stearothermophilus synthetases do not tumble independently in solution, suggesting restricted orientations. Modeling onto a CYT-18/group I intron cocrystal structure indicates that the C-terminal domains of both subunits of the homodimeric protein bind different ends of the intron RNA, with one C-terminal domain having to undergo a large shift on its flexible linker to bind tRNA(Tyr) or the intron RNA on either side of the catalytic domain. The modeling suggests that the C-terminal domain acts together with the N-terminal domain to clamp parts of the intron's catalytic core, that at least one C-terminal domain insertion functions in group I intron binding, and that some C-terminal domain regions bind both tRNA(Tyr) and group I intron RNAs. 相似文献