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排序方式: 共有117条查询结果,搜索用时 20 毫秒
61.
Stoepker C Hain K Schuster B Hilhorst-Hofstee Y Rooimans MA Steltenpool J Oostra AB Eirich K Korthof ET Nieuwint AW Jaspers NG Bettecken T Joenje H Schindler D Rouse J de Winter JP 《Nature genetics》2011,43(2):138-141
DNA interstrand crosslink repair requires several classes of proteins, including structure-specific endonucleases and Fanconi anemia proteins. SLX4, which coordinates three separate endonucleases, was recently recognized as an important regulator of DNA repair. Here we report the first human individuals found to have biallelic mutations in SLX4. These individuals, who were previously diagnosed as having Fanconi anemia, add SLX4 as an essential component to the FA-BRCA genome maintenance pathway. 相似文献
62.
Amos Edelheit 《Studies in history and philosophy of science》2009,40(3):243-257
Francesco Patrizi was a competent Greek scholar, a mathematician, and a Neoplatonic thinker, well known for his sharp critique of Aristotle and the Aristotelian tradition. In this article I shall present, in the first part, the importance of the concept of a three-dimensional space which is regarded as a body, as opposed to the Aristotelian two-dimensional space or interval, in Patrizi’s discussion of physical space. This point, I shall argue, is an essential part of Patrizi’s overall critique of Aristotelian science, in which Epicurean, Stoic, and mainly Neoplatonic elements were brought together, in what seems like an original theory of space and a radical revision of Aristotelian physics. Moreover, I shall try to show Patrizi’s dialectical method of definition, his geometrical argumentation, and trace some of the ideas and terms used by him back to Proclus’ Commentary on Euclid. This text of Proclus, as will be shown in the second part of the article, was also important for Patrizi’s discussion of mathematical space, where Patrizi deals with the status of mathematics and redefines some mathematical concepts such as the point and the line according to his new theory of space. 相似文献
63.
Amos LA 《Cellular and molecular life sciences : CMLS》2008,65(4):509-515
Models commonly used to explain the mechanism of myosin motors typically include a power stroke that is attributed to a conformational
change in the motor domain and amplified by a long lever arm that connects the motor domain to the cargo. Similar models have
proved less enlightening in the case of microtubule motors, for which it may be more helpful to consider models involving
thermally driven mechanisms.
Received 9 November 2007; received after revision 7 December 2007; accepted 11 December 2007 相似文献
64.
Amos CI Wu X Broderick P Gorlov IP Gu J Eisen T Dong Q Zhang Q Gu X Vijayakrishnan J Sullivan K Matakidou A Wang Y Mills G Doheny K Tsai YY Chen WV Shete S Spitz MR Houlston RS 《Nature genetics》2008,40(5):616-622
To identify risk variants for lung cancer, we conducted a multistage genome-wide association study. In the discovery phase, we analyzed 315,450 tagging SNPs in 1,154 current and former (ever) smoking cases of European ancestry and 1,137 frequency-matched, ever-smoking controls from Houston, Texas. For replication, we evaluated the ten SNPs most significantly associated with lung cancer in an additional 711 cases and 632 controls from Texas and 2,013 cases and 3,062 controls from the UK. Two SNPs, rs1051730 and rs8034191, mapping to a region of strong linkage disequilibrium within 15q25.1 containing PSMA4 and the nicotinic acetylcholine receptor subunit genes CHRNA3 and CHRNA5, were significantly associated with risk in both replication sets. Combined analysis yielded odds ratios of 1.32 (P < 1 x 10(-17)) for both SNPs. Haplotype analysis was consistent with there being a single risk variant in this region. We conclude that variation in a region of 15q25.1 containing nicotinic acetylcholine receptors genes contributes to lung cancer risk. 相似文献
65.
Xia B Dorsman JC Ameziane N de Vries Y Rooimans MA Sheng Q Pals G Errami A Gluckman E Llera J Wang W Livingston DM Joenje H de Winter JP 《Nature genetics》2007,39(2):159-161
The Fanconi anemia and BRCA networks are considered interconnected, as BRCA2 gene defects have been discovered in individuals with Fanconi anemia subtype D1. Here we show that a defect in the BRCA2-interacting protein PALB2 is associated with Fanconi anemia in an individual with a new subtype. PALB2-deficient cells showed hypersensitivity to cross-linking agents and lacked chromatin-bound BRCA2; these defects were corrected upon ectopic expression of PALB2 or by spontaneous reversion. 相似文献
66.
Hinch AG Tandon A Patterson N Song Y Rohland N Palmer CD Chen GK Wang K Buxbaum SG Akylbekova EL Aldrich MC Ambrosone CB Amos C Bandera EV Berndt SI Bernstein L Blot WJ Bock CH Boerwinkle E Cai Q Caporaso N Casey G Cupples LA Deming SL Diver WR Divers J Fornage M Gillanders EM Glessner J Harris CC Hu JJ Ingles SA Isaacs W John EM Kao WH Keating B Kittles RA Kolonel LN Larkin E Le Marchand L McNeill LH Millikan RC Murphy A Musani S Neslund-Dudas C Nyante S Papanicolaou GJ Press MF Psaty BM 《Nature》2011,476(7359):170-175
Recombination, together with mutation, gives rise to genetic variation in populations. Here we leverage the recent mixture of people of African and European ancestry in the Americas to build a genetic map measuring the probability of crossing over at each position in the genome, based on about 2.1 million crossovers in 30,000 unrelated African Americans. At intervals of more than three megabases it is nearly identical to a map built in Europeans. At finer scales it differs significantly, and we identify about 2,500 recombination hotspots that are active in people of West African ancestry but nearly inactive in Europeans. The probability of a crossover at these hotspots is almost fully controlled by the alleles an individual carries at PRDM9 (P?value 10(-245)). We identify a 17-base-pair DNA sequence motif that is enriched in these hotspots, and is an excellent match to the predicted binding target of PRDM9 alleles common in West Africans and rare in Europeans. Sites of this motif are predicted to be risk loci for disease-causing genomic rearrangements in individuals carrying these alleles. More generally, this map provides a resource for research in human genetic variation and evolution. 相似文献
67.
Prokaryotic origin of the actin cytoskeleton. 总被引:47,自引:0,他引:47
It was thought until recently that bacteria lack the actin or tubulin filament networks that organize eukaryotic cytoplasm. However, we show here that the bacterial MreB protein assembles into filaments with a subunit repeat similar to that of F-actin-the physiological polymer of eukaryotic actin. By elucidating the MreB crystal structure we demonstrate that MreB and actin are very similar in three dimensions. Moreover, the crystals contain protofilaments, allowing visualization of actin-like strands at atomic resolution. The structure of the MreB protofilament is in remarkably good agreement with the model for F-actin, showing that the proteins assemble in identical orientations. The actin-like properties of MreB explain the finding that MreB forms large fibrous spirals under the cell membrane of rod-shaped cells, where they are involved in cell-shape determination. Thus, prokaryotes are now known to possess homologues both of tubulin, namely FtsZ, and of actin. 相似文献
68.
A R Fersht J P Shi J Knill-Jones D M Lowe A J Wilkinson D M Blow P Brick P Carter M M Waye G Winter 《Nature》1985,314(6008):235-238
The role of complementary hydrogen bonding as a determinant of biological specificity has been examined by protein engineering of the tyrosyl-tRNA synthetase. Deletion of a side chain between enzyme and substrate to leave an unpaired, uncharged hydrogen-bond donor or acceptor weakens binding energy by only 0.5-1.5 kcal mol-1. But the presence of an unpaired and charged donor or acceptor weakens binding by a further approximately 3 kcal mol-1. 相似文献
69.
The binding site for C1q on IgG 总被引:25,自引:0,他引:25
In humoral defence, pathogens are cleared by antibodies acting as adaptor molecules: they bind to antigen and trigger clearance mechanisms such as phagocytosis, antibody-dependent cell-mediated cytotoxicity and complement lysis. The first step in the complement cascade is the binding of C1q to the antibody. There are six heads on C1q, connected by collagen-like stems to a central stalk, and the isolated heads bind to the Fc portion of antibody rather weakly, with an affinity of 100 microM (ref. 3). Binding of antibody to multiple epitopes on an antigenic surface, aggregates the antibody and this facilitates the binding of several C1q heads, leading to an enhanced affinity of about 10 nM (ref. 1). Within the Fc portion of the antibody, C1q binds to the CH2 domain. The interaction is sensitive to ionic strength, and appears to be highly conserved throughout evolution as C1q reacts with IgG from different species (for example see ref. 8). By systematically altering surface residues in the mouse IgG2b isotype, we have localized the binding site for C1q to three side chains, Glu 318, Lys 320 and Lys 322. These residues are relatively conserved in other antibody isotypes, and a peptide mimic of this sequence is able to inhibit complement lysis. We propose that this sequence motif forms a common core in the interactions of IgG and C1q. 相似文献
70.