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排序方式: 共有101条查询结果,搜索用时 46 毫秒
41.
TJ Pugh SD Weeraratne TC Archer DA Pomeranz Krummel D Auclair J Bochicchio MO Carneiro SL Carter K Cibulskis RL Erlich H Greulich MS Lawrence NJ Lennon A McKenna J Meldrim AH Ramos MG Ross C Russ E Shefler A Sivachenko B Sogoloff P Stojanov P Tamayo JP Mesirov V Amani N Teider S Sengupta JP Francois PA Northcott MD Taylor F Yu GR Crabtree AG Kautzman SB Gabriel G Getz N Jäger DT Jones P Lichter SM Pfister TM Roberts M Meyerson SL Pomeroy YJ Cho 《Nature》2012,488(7409):106-110
42.
Piotr Błaszczyk Vladimir Kanovei Karin U. Katz Mikhail G. Katz Semen S. Kutateladze David Sherry 《Foundations of Science》2017,22(4):763-783
Abraham Robinson’s framework for modern infinitesimals was developed half a century ago. It enables a re-evaluation of the procedures of the pioneers of mathematical analysis. Their procedures have been often viewed through the lens of the success of the Weierstrassian foundations. We propose a view without passing through the lens, by means of proxies for such procedures in the modern theory of infinitesimals. The real accomplishments of calculus and analysis had been based primarily on the elaboration of novel techniques for solving problems rather than a quest for ultimate foundations. It may be hopeless to interpret historical foundations in terms of a punctiform continuum, but arguably it is possible to interpret historical techniques and procedures in terms of modern ones. Our proposed formalisations do not mean that Fermat, Gregory, Leibniz, Euler, and Cauchy were pre-Robinsonians, but rather indicate that Robinson’s framework is more helpful in understanding their procedures than a Weierstrassian framework. 相似文献
43.
Although iron is known to be essential for the normal development and health of the central nervous system, abnormal iron deposits are found in and around multiple sclerosis (MS) lesions that themselves are closely associated with the cerebral vasculature. However, the origin of this excess iron is unknown, and it is not clear whether this is one of the primary causative events in the pathogenesis of MS, or simply another consequence of the long-lasting inflammatory conditions. Here, applying a systems biology approach, we propose an additional way for understanding the neurodegenerative component of the disease caused by chronic subclinical extravasation of hemoglobin, in combination with multiple other factors including, but not limited to, dysfunction of different cellular protective mechanisms against extracellular hemoglobin reactivity and oxidative stress. Moreover, such considerations could also shed light on and explain the higher susceptibility of MS patients to a wide range of cardiovascular disorders. 相似文献
44.
Fanchi Meng Vladimir N. Uversky Lukasz Kurgan 《Cellular and molecular life sciences : CMLS》2017,74(17):3069-3090
Computational prediction of intrinsic disorder in protein sequences dates back to late 1970 and has flourished in the last two decades. We provide a brief historical overview, and we review over 30 recent predictors of disorder. We are the first to also cover predictors of molecular functions of disorder, including 13 methods that focus on disordered linkers and disordered protein–protein, protein–RNA, and protein–DNA binding regions. We overview their predictive models, usability, and predictive performance. We highlight newest methods and predictors that offer strong predictive performance measured based on recent comparative assessments. We conclude that the modern predictors are relatively accurate, enjoy widespread use, and many of them are fast. Their predictions are conveniently accessible to the end users, via web servers and databases that store pre-computed predictions for millions of proteins. However, research into methods that predict many not yet addressed functions of intrinsic disorder remains an outstanding challenge. 相似文献
45.
Vladimir Rapoport 《Systemic Practice and Action Research》1989,2(4):433-450
Management organization structure is the most sensitive characteristic displayed by a business organization in the process of its adaptation to the changing environment. It is well-known, however, that excessive changeability of the structure makes the management system unstable and leads to less effective organizational behavior. The author believes that the reason lies in the fact that the structural changes almost always involve the management system's composition too. This shortcoming is rarely found in matrix management of goal-oriented programs. However, application of this type of management structure is limited as complexity of management increases disproportionately. Systems analysis of the problem situation leads to two new conclusions: (a) the variety of management organization structures required by business organizations to adapt to the changing environment can be extended if the organizational relations are regarded as part of organizational/economic symbiosis and their interrelated change; and (b) enhancement of the program component in the matrix structure makes it possible to design stable manage-management structures with a dynamic composition. Implementation of this concept in large-scale business systems brought about essentially new forms of production units' self-organization that became known as state production associations. It makes the large-scale business organizations' structures far less complex and increase their flexibility without disturbing the management systems' resilience. The newly developed principles of organizational design are universal. 相似文献
46.
Koglin A Löhr F Bernhard F Rogov VV Frueh DP Strieter ER Mofid MR Güntert P Wagner G Walsh CT Marahiel MA Dötsch V 《Nature》2008,454(7206):907-911
Non-ribosomal peptide synthetases (NRPS) and polyketide synthases (PKS) found in bacteria, fungi and plants use two different types of thioesterases for the production of highly active biological compounds. Type I thioesterases (TEI) catalyse the release step from the assembly line of the final product where it is transported from one reaction centre to the next as a thioester linked to a 4'-phosphopantetheine (4'-PP) cofactor that is covalently attached to thiolation (T) domains. The second enzyme involved in the synthesis of these secondary metabolites, the type II thioesterase (TEII), is a crucial repair enzyme for the regeneration of functional 4'-PP cofactors of holo-T domains of NRPS and PKS systems. Mispriming of 4'-PP cofactors by acetyl- and short-chain acyl-residues interrupts the biosynthetic system. This repair reaction is very important, because roughly 80% of CoA, the precursor of the 4'-PP cofactor, is acetylated in bacteria. Here we report the three-dimensional structure of a type II thioesterase from Bacillus subtilis free and in complex with a T domain. Comparison with structures of TEI enzymes shows the basis for substrate selectivity and the different modes of interaction of TEII and TEI enzymes with T domains. Furthermore, we show that the TEII enzyme exists in several conformations of which only one is selected on interaction with its native substrate, a modified holo-T domain. 相似文献
47.
Galagan JE Calvo SE Cuomo C Ma LJ Wortman JR Batzoglou S Lee SI Baştürkmen M Spevak CC Clutterbuck J Kapitonov V Jurka J Scazzocchio C Farman M Butler J Purcell S Harris S Braus GH Draht O Busch S D'Enfert C Bouchier C Goldman GH Bell-Pedersen D Griffiths-Jones S Doonan JH Yu J Vienken K Pain A Freitag M Selker EU Archer DB Peñalva MA Oakley BR Momany M Tanaka T Kumagai T Asai K Machida M Nierman WC Denning DW Caddick M Hynes M Paoletti M Fischer R Miller B Dyer P Sachs MS Osmani SA Birren BW 《Nature》2005,438(7071):1105-1115
The aspergilli comprise a diverse group of filamentous fungi spanning over 200 million years of evolution. Here we report the genome sequence of the model organism Aspergillus nidulans, and a comparative study with Aspergillus fumigatus, a serious human pathogen, and Aspergillus oryzae, used in the production of sake, miso and soy sauce. Our analysis of genome structure provided a quantitative evaluation of forces driving long-term eukaryotic genome evolution. It also led to an experimentally validated model of mating-type locus evolution, suggesting the potential for sexual reproduction in A. fumigatus and A. oryzae. Our analysis of sequence conservation revealed over 5,000 non-coding regions actively conserved across all three species. Within these regions, we identified potential functional elements including a previously uncharacterized TPP riboswitch and motifs suggesting regulation in filamentous fungi by Puf family genes. We further obtained comparative and experimental evidence indicating widespread translational regulation by upstream open reading frames. These results enhance our understanding of these widely studied fungi as well as provide new insight into eukaryotic genome evolution and gene regulation. 相似文献
48.
49.
Optimal Variable Weighting for Ultrametric and Additive Trees and K-means Partitioning: Methods and Software 总被引:1,自引:0,他引:1
K -means partitioning. We also describe some new features and improvements to the algorithm proposed by De Soete. Monte Carlo
simulations have been conducted using different error conditions. In all cases (i.e., ultrametric or additive trees, or K-means partitioning), the simulation results indicate that the optimal weighting procedure should be used for analyzing data
containing noisy variables that do not contribute relevant information to the classification structure. However, if the data
involve error-perturbed variables that are relevant to the classification or outliers, it seems better to cluster or partition
the entities by using variables with equal weights. A new computer program, OVW, which is available to researchers as freeware,
implements improved algorithms for optimal variable weighting for ultrametric and additive tree clustering, and includes a
new algorithm for optimal variable weighting for K-means partitioning. 相似文献
50.
V.I.阿诺尔德 《国外科技新书评介》2006,(12):1-2
本书是以当代著名俄罗斯(及前苏联)数学家Amold命名的数学研究问题的汇集,是按俄文原版(2000,莫斯科)英译的第二版平装本。Amold对当代数学发展有重要影响,他主持的莫斯科大学数学讨论班在国际数学界颇负盛名。 相似文献