全文获取类型
收费全文 | 471篇 |
免费 | 38篇 |
出版年
2022年 | 6篇 |
2021年 | 17篇 |
2020年 | 11篇 |
2019年 | 9篇 |
2018年 | 11篇 |
2017年 | 13篇 |
2016年 | 25篇 |
2015年 | 24篇 |
2014年 | 14篇 |
2013年 | 35篇 |
2012年 | 37篇 |
2011年 | 25篇 |
2010年 | 20篇 |
2009年 | 15篇 |
2008年 | 18篇 |
2007年 | 20篇 |
2006年 | 18篇 |
2005年 | 16篇 |
2004年 | 17篇 |
2003年 | 10篇 |
2002年 | 5篇 |
2001年 | 9篇 |
2000年 | 5篇 |
1999年 | 11篇 |
1998年 | 2篇 |
1997年 | 4篇 |
1996年 | 4篇 |
1995年 | 6篇 |
1994年 | 2篇 |
1993年 | 4篇 |
1991年 | 4篇 |
1990年 | 4篇 |
1989年 | 2篇 |
1988年 | 4篇 |
1987年 | 6篇 |
1986年 | 9篇 |
1983年 | 6篇 |
1982年 | 10篇 |
1981年 | 2篇 |
1980年 | 3篇 |
1979年 | 5篇 |
1978年 | 5篇 |
1977年 | 2篇 |
1976年 | 5篇 |
1975年 | 2篇 |
1974年 | 7篇 |
1973年 | 4篇 |
1972年 | 4篇 |
1970年 | 2篇 |
1969年 | 3篇 |
排序方式: 共有509条查询结果,搜索用时 312 毫秒
461.
462.
Jia H Lohr M Jezequel S Davis D Shaikh S Selwood D Zachary I 《Biochemical and biophysical research communications》2001,283(2):469-479
Previous findings suggest that both the Tat polypeptide encoded by HIV-1 and Tat-derived peptides can induce angiogenesis via activation of the KDR receptor for Vascular Endothelial Growth Factor (VEGF). We identified 20 amino acids and 12 amino acid peptides corresponding to the cysteine-rich and basic domains of HIV-1 Tat which inhibited (125)I-VEGF(165) binding to KDR and neuropilin-1 (NP-1) receptors in endothelial cells. Cysteine-rich and basic Tat peptides inhibited VEGF-induced ERK activation and mitogenesis in endothelial cells, and inhibited angiogenesis in vitro at concentrations similar to those which inhibited VEGF receptor binding. These peptides also inhibited proliferation, angiogenesis, and ERK activation induced by basic fibroblast growth factor with similar potency and efficacy. Surprisingly, we found that both cysteine-rich and basic domain Tat peptides strikingly induced apoptosis in endothelial cells, independent of their effects on VEGF and bFGF. Furthermore, we found no evidence for direct biological effects of recombinant Tat on VEGF receptor binding, ERK activation, endothelial cell survival, or mitogenesis. These findings demonstrate novel properties of Tat-derived peptides and indicate that their major effect in endothelial cells is apoptosis independent of specific inhibition of VEGF receptor activation. 相似文献
463.
464.
The facile synthesis of high molecular weight water-soluble O-glycopolypeptide polymers by the ring-opening polymerization of their corresponding N-carboxyanhydride (NCA) in very high yield (overall yield > 70%) is reported. The per-acetylated-O-glycosylated lysine-NCA monomers, synthesized using stable glycosyl donors and a commercially available protected amino acid in very high yield, was polymerized using commercially available amine initiators. The synthesized water-soluble glycopolypeptides were found to be α-helical in aqueous solution. However, we were able to control the secondary conformation of the glycopolypeptides (α-helix vs nonhelical structures) by polymerizing racemic amino acid glyco NCAs. We have also investigated the binding of the glycopolypeptide poly(α-manno-O-lys) with the lectin Con-A using precipitation and hemagglutination assays as well as by isothermal titration calorimetry (ITC). The ITC results clearly show that the binding process is enthalpy driven for both α-helical and nonhelical structures, with negative entropic contribution. Binding stoichiometry for the glycopolypeptide poly(α-manno-O-lys) having a nonhelical structure was slightly higher as compared to the corresponding polypeptide which adopted an α-helical structure. 相似文献
465.
466.
4-Thialysine (S-(2-aminoethyl)-l-cysteine) is an analog of lysine. It has been used as an alternative substrate for lysine in enzymatic reactions. Site-directed
isotopomers are often needed for elucidation of mechanism of reactions. 4-Thialysine can be synthesized by reacting cysteine
with 2-bromoethylamine, an important reagent in chemical-modification rescue (CMR) of proteins. Here, we present the synthesis
of 4-thia-[6-13C]lysine, one of the isotopomers of 4-thialysine, from commercially available starting material [2-13C]glycine via formation of five intermediates including 2-amino[2-13C]ethanol and 2-bromo[1-13C]ethylamine. The compounds were characterized using various spectroscopic techniques. Moreover, we discuss that our strategy
would provide access to site-directed isotopomers of 2-aminoethanol, 2-bromoethylamine and 4-thialysine. Biological activity
of 4-thia-[6-13C]lysine was tested in the enzymatic reaction of lysine 5,6-aminomutase. 相似文献
467.
468.
Ramakrishnan V Jagannathan S Shaikh AR Rajagopalan R 《Journal of biomolecular structure & dynamics》2012,29(4):743-756
The dynamics of a protein plays an important role in protein functionality. Here, we examine the differences in the dynamics of a minimally restructuring protein, EcoRI, when it is bound to its cognate DNA and to a noncognate sequence which differs by just a single basepair. Molecular dynamics simulations of the complexes and essential dynamics analyses reveal that the overall dynamics of the protein subunits change from a coordinated motion in the cognate complex to a scrambled motion in the noncognate complex. This dynamical difference extends to the protein-DNA interface where EcoRI tries to constrict the DNA in the cognate complex. In the noncognate complex, absence of the constricting motion of interfacial residues, overall change in backbone dynamics and structural relaxation of the arms enfolding the DNA leave the DNA less-kinked relative to the situation in the cognate complex, thus indicating that the protein is poised for linear diffusion along the DNA rather than for catalytic action. In a larger context, the results imply that the DNA sequences dictate protein dynamics and that when a protein chances upon the recognition sequence some of the key domains of the protein undergo dynamical changes that prepare the protein for eventual catalytic action. 相似文献
469.
Rockett BD Teague H Harris M Melton M Williams J Wassall SR Shaikh SR 《Journal of lipid research》2012,53(4):674-685
Fish oil (FO) targets lipid microdomain organization to suppress T-cell and macrophage function; however, little is known about this relationship with B cells, especially at the animal level. We previously established that a high FO dose diminished mouse B-cell lipid raft microdomain clustering induced by cross-linking GM1. To establish relevance, here we tested a FO dose modeling human intake on B-cell raft organization relative to a control. Biochemical analysis revealed more docosahexaenoic acid (DHA) incorporated into phosphatidylcholines than phosphatidylethanolamines of detergent-resistant membranes, consistent with supporting studies with model membranes. Subsequent imaging experiments demonstrated that FO increased raft size, GM1 expression, and membrane order upon cross-linking GM1 relative to no cross-linking. Comparative in vitro studies showed some biochemical differences from in vivo measurements but overall revealed that DHA, but not eicosapentaenoic acid (EPA), increased membrane order. Finally, we tested the hypothesis that disrupting rafts with FO would suppress B-cell responses ex vivo. FO enhanced LPS-induced B-cell activation but suppressed B-cell stimulation of transgenic naive CD4(+) T cells. Altogether, our studies with B cells support an emerging model that FO increases raft size and membrane order accompanied by functional changes; furthermore, the results highlight differences in EPA and DHA bioactivity. 相似文献
470.
Bandgar BP Adsul LK Chavan HV Jalde SS Shringare SN Shaikh R Meshram RJ Gacche RN Masand V 《Bioorganic & medicinal chemistry letters》2012,22(18):5839-5844
A novel series of 3-(substituted)-aryl-5-(9-methyl-3-carbazole)-1H-2-pyrazolines (5a-o) has been synthesized and the structures of newly synthesized compounds were characterized by IR, (1)H NMR and mass spectral analysis. All the synthesized compounds were evaluated for their in vitro and in vivo anti-inflammatory activity, and also for their antioxidant activity. Compounds 5b, 5c, 5d and 5n were found to be selective COX-2 inhibitors. Compound 5c was found to potent inhibitor of the carrageenin induced paw edema in rats. Most of the compounds exhibited good DPPH and superoxide radical scavenging activity, while compounds 5c, 5d, 5i and 5k exhibited good hydroxyl radical scavenging activity. Molecular docking result, along with the biological assay data, suggested that compound 5c was a potential anti-inflammatory agent. 相似文献