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Small molecule inhibitors have a powerful blocking action on viral polymerases. The bioavailability of the inhibitor, nevertheless, often raise a significant selectivity constraint and may substantially limit the efficacy of therapy. Phosphonoacetic acid has long been known to possess a restricted potential to block DNA biosynthesis. In order to achieve a better affinity, this compound has been linked with natural nucleotide at different positions. The structural context of the resulted conjugates has been found to be crucial for the acquisition by DNA polymerases. We show that nucleobase-conjugated phosphonoacetic acid is being accepted, but this alters the processivity of DNA polymerases. The data presented here not only provide a mechanistic rationale for a switch in the mode of DNA synthesis, but also highlight the nucleobase-targeted nucleotide functionalization as a route for enhancing the specificity of small molecule inhibitors.  相似文献   
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Ohne ZusammenfassungDas Referat bezieht sich auf den Zeitraum vom 1. Jänner bis 1. Juni 1890.  相似文献   
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ATP diphosphohydrolase activity and inorganic pyrophosphatase reached two maxima during cultivation of the low- and high-producing variant ofStreptomyces aureofaciens under conditions of phosphate limitation,i.e. after 30 and 70 h of cultivation. Increased levels of inorganic phosphate in a medium inhibitory to biosynthesis of chlortetracycline markedly decreased the levels of both enzymes. The ATP diphosphohydrolase activity was detected both in the supernatant and membrane fractions of the cell-free preparation of the mycelium.  相似文献   
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Floral meristems of Lolium and Festuca grasses give a 5- to 19-fold enhancement in yield of extracted DNA in comparison with leaves. Meristems also provide highly pure DNA samples. The method could be useful for applications in molecular genetics in many species of the Gramineae. Received: 14 April 1998 / Revision received: 8 June 1998 / Accepted: 10 July 1998  相似文献   
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The Daphnia longispina complex contains some of the most common water flea species in the northern hemisphere, and has been a model organism for many ecological and evolutionary studies. Nevertheless, the systematics and nomenclature of this group, in particular its Palaearctic members, have been in flux for the past 150 years; this hinders the correct interpretation of scientific results and promotes the erroneous use of species names. We revise the systematics of this species complex based on mitochondrial sequence variation (12S rDNA and COI) of representative populations across Europe, with a special focus on samples from type localities of the respective taxa. Combining genetic evidence and morphological assignments of analysed individuals, we propose a comprehensive revision of the European members of the D. longispina complex. We show that D. hyalina and D. rosea morphotypes have evolved several times independently, and we find no evidence to maintain these morphotypes as distinct biological species. Alpine individuals described as D. zschokkei are conspecific with the above-mentioned lineage. We suggest that this morphologically and ecologically plastic but genetically uniform hyalina–rosea–zschokkei clade should be identified as D. longispina (O. F. Müller, 1776). The valid name of Fennoscandian individuals labelled D. longispina sensu stricto in the recent literature is D. lacustris G. O. Sars, 1862. Additionally, we discovered another divergent lineage of this group, likely an undescribed species, in southern Norway. Our results present a solution for several prevailing taxonomic problems in the genus Daphnia , and have broad implications for interpretation of biogeographical patterns, and ecological and evolutionary studies.  相似文献   
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