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51.
52.
Synthesis and evaluation of some properties of chimeric oligomers containing PNA and phosphono-PNA residues. 总被引:3,自引:0,他引:3
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V A Efimov M V Choob A A Buryakova A L Kalinkina O G Chakhmakhcheva 《Nucleic acids research》1998,26(2):566-575
In an attempt to improve physico-chemical and biological properties of peptide nucleic acids (PNAs), particularly water solubility and cellular uptake, the synthesis of chimeric oligomers consisted of PNA and phosphono-PNA analogues (pPNAs) bearing the four natural nucleobases has been accomplished. To produce these chimeras, pPNA monomers of two types containing N-(2-hydroxyethyl)phosphonoglycine, or N-(2-aminoethyl)phosphonoglycine backbone, were used in conjunction with PNA monomers representing derivatives of N-(2-aminoethyl)glycine, or N-(2-hydroxyethyl)glycine. The oligomers obtained were composed of either PNA and pPNA stretches or alternating PNA and pPNA monomers. The examination of hybridization properties of PNA-pPNA chimeras to DNA and RNA complementary strands in comparison with pure PNAs, and pPNAs as well as DNA-pPNA hybrids and DNA fragments confirmed that these chimeras form stable complexes with complementary DNA and RNA fragments. They were found to be resistant to degradation by nucleases. All these properties together with good solubility in water make PNA-pPNA hybrids promising for further evaluation as potential therapeutic agents. 相似文献
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Pipirou Z Bottrill AR Svistunenko DA Efimov I Basran J Mistry SC Cooper CE Raven EL 《Biochemistry》2007,46(46):13269-13278
We have previously shown that introduction of an engineered Met160 residue in ascorbate peroxidase (S160M variant) leads to the formation of a covalent link between Met160 and the heme vinyl group [Metcalfe, C. L., et al. (2004) J. Am. Chem. Soc. 126, 16242-16248]. In this work, we have used electronic spectroscopy, HPLC, and mass spectrometry to show that the introduction of a tyrosine residue at the same position (S160Y variant) leads, similarly, to the formation of a heme-tyrosine covalent link in an autocatalytic reaction that also leads to formation of a second covalent link from the heme to Trp41 [Pipirou, Z., et al. (2007) Biochemistry 46, 2174-2180]. Stopped-flow and EPR data implicate the involvement of a tyrosyl radical in the reaction mechanism. The results indicate that the heme can support the formation of different types of covalent links under appropriate conditions. The generality of this idea is discussed in the context of other heme enzymes. 相似文献
55.
A database of 926 (α + β)-proteins and (α + β)-domains containing abCd units, including 401 non-homologous, was compiled from the Protein Data Bank (total of 2636 PDB entries). A novel structural tree of this structural class of proteins was constructed to include 286 possible polypeptide chain folds. A structural classification of (α + β)-proteins containing abCd unit was developed on the basis of the structural tree. The database and the structural tree are available at http://strees.protres.ru/. 相似文献
56.
As members of the family of heme-dependent enzymes, the heme dioxygenases are differentiated by virtue of their ability to catalyze the oxidation of l-tryptophan to N-formylkynurenine, the first and rate-limiting step in tryptophan catabolism. In the past several years, there have been a number of important developments that have meant that established proposals for the reaction mechanism in the heme dioxygenases have required reassessment. This focused review presents a summary of these recent advances, written from a structural and mechanistic perspective. It attempts to present answers to some of the long-standing questions, to highlight as yet unresolved issues, and to explore the similarities and differences of other well-known catalytic heme enzymes such as the cytochromes P450, NO synthase, and peroxidases. 相似文献
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A convenient route of obtaining recombinant human proinsulin from the hybrid protein produced by the bacteria was developed. Chimeric protein was prepared by ultra- or gel-filtration, immobilized on thiol-support at cysteine residues and cleaved by cyanogen bromide to liberate purified proinsulin. Conditions of treatment hybrid protein with cyanogen bromide at methionine residues without affecting disulfide bonds between proinsulin and support are described. Proinsulin with correct disulfide bonds, directly obtained from polymer--attached polypeptide, followed was converted into insulin. 相似文献
59.
A S Efimov M F Guly? N D Dzvonkevich N F Shevtsova A V Whcherbak 《Ukrainski? biokhimicheski? zhurnal》1980,52(6):767-770
Application of carbostimulin, the preparation stimulating CO2 fixation in tissues, in a complex therapy of diabetes mellitus patients rises the CO2 level, restores the total content of alpha-ketoacids and free amino acids in blood, increases (within the physiological normal limits) the urea content in blood and urine of diabetes mellitus patients. 相似文献
60.
G. A. Efimov J. M. H. Raats R. G. S. Chirivi J. W. G. van Rosmalen S. A. Nedospasov 《Molecular Biology》2017,51(6):921-926
Tumor necrosis factor (TNF) is a proinflammatory cytokine implicated in pathogenesis of multiple autoimmune and inflammatory diseases. Anti-TNF therapy has revolutionized the therapeutic paradigms of autoimmune diseases and became one of the most successful examples of the clinical use of monoclonal antibodies. Currently, anti-TNF therapy is used by millions of patients worldwide. At the moment, fully human anti-TNF antibody Adalimumab is the best-selling anti-cytokine drug in the world. Here, we present a story about a highly potent anti-TNF monoclonal antibody initially characterized more than 20 years ago and further developed into chimeric and humanized versions. We present comparative analysis of this antibody with Infliximab and Adalimumab. 相似文献