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61.
Zou P Pinotsis N Lange S Song YH Popov A Mavridis I Mayans OM Gautel M Wilmanns M 《Nature》2006,439(7073):229-233
The Z-disk of striated and cardiac muscle sarcomeres is one of the most densely packed cellular structures in eukaryotic cells. It provides the architectural framework for assembling and anchoring the largest known muscle filament systems by an extensive network of protein-protein interactions, requiring an extraordinary level of mechanical stability. Here we show, using X-ray crystallography, how the amino terminus of the longest filament component, the giant muscle protein titin, is assembled into an antiparallel (2:1) sandwich complex by the Z-disk ligand telethonin. The pseudosymmetric structure of telethonin mediates a unique palindromic arrangement of two titin filaments, a type of molecular assembly previously found only in protein-DNA complexes. We have confirmed its unique architecture in vivo by protein complementation assays, and in vitro by experiments using fluorescence resonance energy transfer. The model proposed may provide a molecular paradigm of how major sarcomeric filaments are crosslinked, anchored and aligned within complex cytoskeletal networks. 相似文献
62.
Wang J Soisson SM Young K Shoop W Kodali S Galgoci A Painter R Parthasarathy G Tang YS Cummings R Ha S Dorso K Motyl M Jayasuriya H Ondeyka J Herath K Zhang C Hernandez L Allocco J Basilio A Tormo JR Genilloud O Vicente F Pelaez F Colwell L Lee SH Michael B Felcetto T Gill C Silver LL Hermes JD Bartizal K Barrett J Schmatz D Becker JW Cully D Singh SB 《Nature》2006,441(7091):358-361
Bacterial infection remains a serious threat to human lives because of emerging resistance to existing antibiotics. Although the scientific community has avidly pursued the discovery of new antibiotics that interact with new targets, these efforts have met with limited success since the early 1960s. Here we report the discovery of platensimycin, a previously unknown class of antibiotics produced by Streptomyces platensis. Platensimycin demonstrates strong, broad-spectrum Gram-positive antibacterial activity by selectively inhibiting cellular lipid biosynthesis. We show that this anti-bacterial effect is exerted through the selective targeting of beta-ketoacyl-(acyl-carrier-protein (ACP)) synthase I/II (FabF/B) in the synthetic pathway of fatty acids. Direct binding assays show that platensimycin interacts specifically with the acyl-enzyme intermediate of the target protein, and X-ray crystallographic studies reveal that a specific conformational change that occurs on acylation must take place before the inhibitor can bind. Treatment with platensimycin eradicates Staphylococcus aureus infection in mice. Because of its unique mode of action, platensimycin shows no cross-resistance to other key antibiotic-resistant strains tested, including methicillin-resistant S. aureus, vancomycin-intermediate S. aureus and vancomycin-resistant enterococci. Platensimycin is the most potent inhibitor reported for the FabF/B condensing enzymes, and is the only inhibitor of these targets that shows broad-spectrum activity, in vivo efficacy and no observed toxicity. 相似文献
63.
Homologous recombination has a crucial function in the repair of DNA double-strand breaks and in faithful chromosome segregation. The mechanism of homologous recombination involves the search for homology and invasion of the ends of a broken DNA molecule into homologous duplex DNA to form a cross-stranded structure, a Holliday junction (HJ). A HJ is able to undergo branch migration along DNA, generating increasing or decreasing lengths of heteroduplex. In both prokaryotes and eukaryotes, the physical evidence for HJs, the key intermediate in homologous recombination, was provided by electron microscopy. In bacteria there are specialized enzymes that promote branch migration of HJs. However, in eukaryotes the identity of homologous recombination branch-migration protein(s) has remained elusive. Here we show that Rad54, a Swi2/Snf2 protein, binds HJ-like structures with high specificity and promotes their bidirectional branch migration in an ATPase-dependent manner. The activity seemed to be conserved in human and yeast Rad54 orthologues. In vitro, Rad54 has been shown to stimulate DNA pairing of Rad51, a key homologous recombination protein. However, genetic data indicate that Rad54 protein might also act at later stages of homologous recombination, after Rad51 (ref. 13). Novel DNA branch-migration activity is fully consistent with this late homologous recombination function of Rad54 protein. 相似文献
64.
J. L. Kennedy J. W. Snyder R. B. Otero 《Cellular and molecular life sciences : CMLS》1974,30(10):1147-1149
Zusammenfassung Nachweis, dass die Transformation vonNeisseria catarrhalis sich mit Antibiotika und Chemikalien hemmen lässt, die ihrerseits die Eiweiss-und Zellwandsynthese hemmen. Daraus wird geschlossen, dass Eiweiss- und Zellwandsynthese zur Transformation nötig sind.
Eastern Kentucky University Grant No. 05-03-422-41 was the sole support of this project and was given to the last author. 相似文献
Eastern Kentucky University Grant No. 05-03-422-41 was the sole support of this project and was given to the last author. 相似文献
65.
Basilio de Bragana Pereira Ricardo Cesar Otero Coqueiro Antonio Horcio Vincente Perrota 《Journal of forecasting》1989,8(3):343-348
This paper presents a method of combining subjective information from open-market operators with results from a time-series forecasting model. Empirical results of forecasts for interest rates of bank reserves are presented. 相似文献
66.
Olga E. Scaramuzzi C. A. Baile J. Mayer 《Cellular and molecular life sciences : CMLS》1971,27(3):256-257
Zusammenfassung Nachweis der Wirkung verschiedener Prostaglandine auf die Nahrungsaufnahme bei der Ratte.
This work was supported in part by grants-in-aid from the National Institute of Neurological Diseases and Blindness No. NB-01941 and the National Institute of Arthritis and Metabolie Diseases No. AM-02911; and the Fund for Research and Teaching, Department of Nutrition, Harvard School of Public Health. 相似文献
This work was supported in part by grants-in-aid from the National Institute of Neurological Diseases and Blindness No. NB-01941 and the National Institute of Arthritis and Metabolie Diseases No. AM-02911; and the Fund for Research and Teaching, Department of Nutrition, Harvard School of Public Health. 相似文献
67.
Geology and palaeontology of the Upper Miocene Toros-Menalla hominid locality,Chad 总被引:13,自引:0,他引:13
Vignaud P Duringer P Mackaye HT Likius A Blondel C Boisserie JR De Bonis L Eisenmann V Etienne ME Geraads D Guy F Lehmann T Lihoreau F Lopez-Martinez N Mourer-Chauviré C Otero O Rage JC Schuster M Viriot L Zazzo A Brunet M 《Nature》2002,418(6894):152-155
All six known specimens of the early hominid Sahelanthropus tchadensis come from Toros-Menalla site 266 (TM 266), a single locality in the Djurab Desert, northern Chad, central Africa. Here we present a preliminary analysis of the palaeontological and palaeoecological context of these finds. The rich fauna from TM 266 includes a significant aquatic component such as fish, crocodiles and amphibious mammals, alongside animals associated with gallery forest and savannah, such as primates, rodents, elephants, equids and bovids. The fauna suggests a biochronological age between 6 and 7 million years. Taken together with the sedimentological evidence, the fauna suggests that S. tchadensis lived close to a lake, but not far from a sandy desert, perhaps the oldest record of desert conditions in the Neogene of northern central Africa. 相似文献
68.
Zusammenfassung Antikörper mit einer gegen kompetenteN. catarrhalis gerichteten Spezifität vermindern deren Transformationshäufigkeit bedeutend. Diese Beobachtung könnte auf die Existenz von Membranrezeptoren für transformierende Wildtyp-DNS hinweisen.
This investigation was supported by the Research Corporation of Chicago No. 40-84 and Eastern Kentucky University Research Grant No. 05-03-422-41. 相似文献
This investigation was supported by the Research Corporation of Chicago No. 40-84 and Eastern Kentucky University Research Grant No. 05-03-422-41. 相似文献
69.
Sleep affects learning and development in humans and other animals, but the role of sleep in developmental learning has never been examined. Here we show the effects of night-sleep on song development in the zebra finch by recording and analysing the entire song ontogeny. During periods of rapid learning we observed a pronounced deterioration in song structure after night-sleep. The song regained structure after intense morning singing. Daily improvement in similarity to the tutored song occurred during the late phase of this morning recovery; little further improvement occurred thereafter. Furthermore, birds that showed stronger post-sleep deterioration during development achieved a better final imitation. The effect diminished with age. Our experiments showed that these oscillations were not a result of sleep inertia or lack of practice, indicating the possible involvement of an active process, perhaps neural song-replay during sleep. We suggest that these oscillations correspond to competing demands of plasticity and consolidation during learning, creating repeated opportunities to reshape previously learned motor skills. 相似文献
70.
Martin J Han C Gordon LA Terry A Prabhakar S She X Xie G Hellsten U Chan YM Altherr M Couronne O Aerts A Bajorek E Black S Blumer H Branscomb E Brown NC Bruno WJ Buckingham JM Callen DF Campbell CS Campbell ML Campbell EW Caoile C Challacombe JF Chasteen LA Chertkov O Chi HC Christensen M Clark LM Cohn JD Denys M Detter JC Dickson M Dimitrijevic-Bussod M Escobar J Fawcett JJ Flowers D Fotopulos D Glavina T Gomez M Gonzales E Goodstein D Goodwin LA Grady DL Grigoriev I Groza M Hammon N Hawkins T 《Nature》2004,432(7020):988-994