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排序方式: 共有252条查询结果,搜索用时 484 毫秒
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Yayuan Qin Yao Shen Changle Liu Hongliang Wo Yonghao Gao Yu Feng Xiaowen Zhang Gaofeng Ding Yiqing Gu Qisi Wang Shoudong Shen Helen C.Walker Robert Bewley Jianhui Xu Martin Boehm Paul Steffens Seiko Ohira-Kawamura Naoki Murai Astrid Schneidewind Xin Tong Gang Chen Jun Zhao 《科学通报(英文版)》2022,(1):38-44
We report thermodynamic and neutron scattering measurements of the triangular-lattice quantum Ising magnet TmMgGaO4 in longitudinal magnetic fields.Our experime... 相似文献
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Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase 总被引:2,自引:0,他引:2
Bryant HE Schultz N Thomas HD Parker KM Flower D Lopez E Kyle S Meuth M Curtin NJ Helleday T 《Nature》2005,434(7035):913-917
Poly(ADP-ribose) polymerase (PARP1) facilitates DNA repair by binding to DNA breaks and attracting DNA repair proteins to the site of damage. Nevertheless, PARP1-/- mice are viable, fertile and do not develop early onset tumours. Here, we show that PARP inhibitors trigger gamma-H2AX and RAD51 foci formation. We propose that, in the absence of PARP1, spontaneous single-strand breaks collapse replication forks and trigger homologous recombination for repair. Furthermore, we show that BRCA2-deficient cells, as a result of their deficiency in homologous recombination, are acutely sensitive to PARP inhibitors, presumably because resultant collapsed replication forks are no longer repaired. Thus, PARP1 activity is essential in homologous recombination-deficient BRCA2 mutant cells. We exploit this requirement in order to kill BRCA2-deficient tumours by PARP inhibition alone. Treatment with PARP inhibitors is likely to be highly tumour specific, because only the tumours (which are BRCA2-/-) in BRCA2+/- patients are defective in homologous recombination. The use of an inhibitor of a DNA repair enzyme alone to selectively kill a tumour, in the absence of an exogenous DNA-damaging agent, represents a new concept in cancer treatment. 相似文献
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Egalitarianism in young children 总被引:1,自引:0,他引:1
Human social interaction is strongly shaped by other-regarding preferences, that is, a concern for the welfare of others. These preferences are important for a unique aspect of human sociality-large scale cooperation with genetic strangers-but little is known about their developmental roots. Here we show that young children's other-regarding preferences assume a particular form, inequality aversion that develops strongly between the ages of 3 and 8. At age 3-4, the overwhelming majority of children behave selfishly, whereas most children at age 7-8 prefer resource allocations that remove advantageous or disadvantageous inequality. Moreover, inequality aversion is strongly shaped by parochialism, a preference for favouring the members of one's own social group. These results indicate that human egalitarianism and parochialism have deep developmental roots, and the simultaneous emergence of altruistic sharing and parochialism during childhood is intriguing in view of recent evolutionary theories which predict that the same evolutionary process jointly drives both human altruism and parochialism. 相似文献
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Wingert RA Galloway JL Barut B Foott H Fraenkel P Axe JL Weber GJ Dooley K Davidson AJ Schmid B Schmidt B Paw BH Shaw GC Kingsley P Palis J Schubert H Chen O Kaplan J Zon LI;Tübingen Screen Consortium 《Nature》2005,436(7053):1035-1039
Iron is required to produce haem and iron-sulphur (Fe-S) clusters, processes thought to occur independently. Here we show that the hypochromic anaemia in shiraz (sir) zebrafish mutants is caused by deficiency of glutaredoxin 5 (grx5), a gene required in yeast for Fe-S cluster assembly. We found that grx5 was expressed in erythroid cells of zebrafish and mice. Zebrafish grx5 rescued the assembly of grx5 yeast Fe-S, showing that the biochemical function of grx5 is evolutionarily conserved. In contrast to yeast, vertebrates use iron regulatory protein 1 (IRP1) to sense intracellular iron and regulate mRNA stability or the translation of iron metabolism genes. We found that loss of Fe-S cluster assembly in sir animals activated IRP1 and blocked haem biosynthesis catalysed by aminolaevulinate synthase 2 (ALAS2). Overexpression of ALAS2 RNA without the 5' iron response element that binds IRP1 rescued sir embryos, whereas overexpression of ALAS2 including the iron response element did not. Further, antisense knockdown of IRP1 restored sir embryo haemoglobin synthesis. These findings uncover a connection between haem biosynthesis and Fe-S clusters, indicating that haemoglobin production in the differentiating red cell is regulated through Fe-S cluster assembly. 相似文献
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Van Steen K McQueen MB Herbert A Raby B Lyon H Demeo DL Murphy A Su J Datta S Rosenow C Christman M Silverman EK Laird NM Weiss ST Lange C 《Nature genetics》2005,37(7):683-691
The Human Genome Project and its spin-offs are making it increasingly feasible to determine the genetic basis of complex traits using genome-wide association studies. The statistical challenge of analyzing such studies stems from the severe multiple-comparison problem resulting from the analysis of thousands of SNPs. Our methodology for genome-wide family-based association studies, using single SNPs or haplotypes, can identify associations that achieve genome-wide significance. In relation to developing guidelines for our screening tools, we determined lower bounds for the estimated power to detect the gene underlying the disease-susceptibility locus, which hold regardless of the linkage disequilibrium structure present in the data. We also assessed the power of our approach in the presence of multiple disease-susceptibility loci. Our screening tools accommodate genomic control and use the concept of haplotype-tagging SNPs. Our methods use the entire sample and do not require separate screening and validation samples to establish genome-wide significance, as population-based designs do. 相似文献
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Summary In shoots ofLinum perenne apical growth was observed at both ends of the fibres. Their rounded tips, rich in protoplasm, protude into the middle lamellae of adjacent fibres or parenchyma cells. In addition to their apical growth, the fibre walls undergo symplastic growth with the walls of neighbouring cells. The formation of the pointed ends of fully developed fibres is described. 相似文献