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排序方式: 共有103条查询结果,搜索用时 15 毫秒
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George Nicolae Daniel Ion George Mihai Nitulescu Costin Ioan Popescu 《Bioorganic & medicinal chemistry letters》2019,29(18):2527-2534
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), also known as Apo2L, has been investigated in the past decade for its promising anticancer activity due to its ability to selectively induce apoptosis in tumoral cells by binding to TRAIL receptors (TRAIL-R). Macromolecules such as agonistic monoclonal antibodies and recombinant TRAIL have not proven efficacious in clinical studies, therefore several small molecules acting as TRAIL-R agonists are emerging in the scientific literature. In this work we focus on systemizing these drug molecules described in the past years, in order to better understand and predict the requirements for a novel anti-tumoral therapy based on the TRAIL-R-induced apoptotic mechanism. 相似文献
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Plymale DR Comardelle AM Fermi CD Martin DS Costin JM Norris CH Tencza SB Mietzner TA Montelaro RC Garry RF 《Peptides》1999,20(11):1275-1283
The mechanism by which human immunodeficiency virus type 1 induces depletion of CD4+ T-lymphocytes remains controversial, but may involve cytotoxic viral proteins. Synthetic peptides (lentivirus lytic peptide type 1) corresponding to the carboxyl terminus of the human immunodeficiency virus type 1 transmembrane glycoprotein induce cytopathology at concentrations of 100 nM and above. At these concentrations lentivirus lytic peptide type 1 disrupts mitochondrial integrity of CD4+ T-lymphoblastoid cells and induces other changes characteristic of necrosis. In contrast, at concentrations of 20 nM, lentivirus lytic peptide type 1 potently induces apoptosis. Thus, the mechanism by which human immunodeficiency virus type 1 mediates cell death, necrosis or apoptosis, may depend, in part, on the tissue concentration of transmembrane glycoprotein. 相似文献
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Greggio E Bergantino E Carter D Ahmad R Costin GE Hearing VJ Clarimon J Singleton A Eerola J Hellström O Tienari PJ Miller DW Beilina A Bubacco L Cookson MR 《Journal of neurochemistry》2005,93(1):246-256
Tyrosinase is a key enzyme in the synthesis of melanin in skin and hair and has also been proposed to contribute to the formation of neuromelanin (NM). The presence of NM, which is biochemically similar to melanin in peripheral tissues, identifies groups of neurons susceptible in Parkinson's disease (PD). Whether tyrosinase is beneficial or detrimental to neurons is unclear; whilst the enzyme activity of tyrosinase generates dopamine-quinones and other oxidizing compounds, NM may form a sink for such radical species. In the present study, we demonstrated that tyrosinase is expressed at low levels in the human brain. We found that mRNA, protein and enzyme activity are all present but at barely detectable levels. In cell culture systems, expression of tyrosinase increases neuronal susceptibility to oxidizing conditions, including dopamine itself. We related these in vitro observations to the human disease by assessing whether there was any genetic association between the gene encoding tyrosinase and idiopathic PD. We found neither genotypic or haplotypic association with three polymorphic markers of the gene. This argues against a strong genetic association between tyrosinase and PD, although the observed contribution to cellular toxicity suggests that a biochemical association is likely. 相似文献
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Niels H. Andersen C.Richard Costin C.Michael Kramer Yoshimoto Ohta Siegfried Huneck 《Phytochemistry》1973,12(11):2709-2716
Two isomeric olefins, α- and β-barbatene, apparently of a new tricyclic sesquiterpene skeleton (that of gymnomitrol), have been found in the liverworts Barbilophozia barbata, B. floerkei, B. lycopodioides, and B. attenuata. Additional components identified are alkanes, calamenene and α-alaskene. GLC suggests the presence of caryophyllene, longifolene, bazzanene and α-cedrene in minor amounts. 相似文献
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Joshua M. Costin Ekachai Jenwitheesuk Shee-Mei Lok Elizabeth Hunsperger Kelly A. Conrads Krystal A. Fontaine Craig R. Rees Michael G. Rossmann Sharon Isern Ram Samudrala Scott F. Michael 《PLoS neglected tropical diseases》2010,4(6)
Viral fusogenic envelope proteins are important targets for the development of inhibitors of viral entry. We report an approach for the computational design of peptide inhibitors of the dengue 2 virus (DENV-2) envelope (E) protein using high-resolution structural data from a pre-entry dimeric form of the protein. By using predictive strategies together with computational optimization of binding “pseudoenergies”, we were able to design multiple peptide sequences that showed low micromolar viral entry inhibitory activity. The two most active peptides, DN57opt and 1OAN1, were designed to displace regions in the domain II hinge, and the first domain I/domain II beta sheet connection, respectively, and show fifty percent inhibitory concentrations of 8 and 7 µM respectively in a focus forming unit assay. The antiviral peptides were shown to interfere with virus:cell binding, interact directly with the E proteins and also cause changes to the viral surface using biolayer interferometry and cryo-electron microscopy, respectively. These peptides may be useful for characterization of intermediate states in the membrane fusion process, investigation of DENV receptor molecules, and as lead compounds for drug discovery. 相似文献