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91.
92.
DNA错配修复(mismatch repair, MMR)功能缺失是确认的肿瘤发病机制之一. 随着研究的深入以及临床诊断治疗的要求, 有必要从整体上对肿瘤的错配修复功能状态作出评价. 以M13mp2噬菌体及其衍生株和E. coli大肠杆菌为材料, 以lacZα为报告基因, 构建含有错配碱基的异源双链DNA分子. 提取错配修复功能完整细胞株(TK6)和错配修复功能缺陷细胞株(Lovo)的全细胞蛋白, 经大T抗原依赖性SV-40 DNA复制检测, 证实其生物学功能保持完整后与构建成功的异源双链DNA分子共同作用, 发现TK6对双碱基缺失del(2)的修复效率超过60%, 对单碱基错配G·G的修复效率超过50%; 而Lovo对双碱基缺失del(2)的修复效率低于20%, 对单碱基错配G·G的修复效率低于10%. 以异源双链DNA为待修复模板, 以细胞株TK6和Lovo分别作为MMR功能完善和缺陷表型的参照, 建立体外错配修复功能分析模型. 应用该模型检测1例具有微卫星不稳定性表型的HNPCC病人肿瘤组织, 发现其MMR功能丧失; 而检测1例微卫星稳定的散发性直肠癌病人肿瘤组织, 发现其具有MMR功能. 结果表明该模型可用于体外检测各种肿瘤细胞和/或组织的错配修复功能. 为肿瘤发病机制的研究提供了可靠的方法, 对进一步了解错配修复功能状态在各种类型肿瘤中的作用有非常重要的意义. 相似文献
93.
Alan Richardson 《Studies in history and philosophy of science》2003,34(1):165-182
On an ordinary view of the relation of philosophy of science to science, science serves only as a topic for philosophical reflection, reflection that proceeds by its own methods and according to its own standards. This ordinary view suggests a way of writing a global history of philosophy of science that finds substantially the same philosophical projects being pursued across widely divergent scientific eras. While not denying that this view is of some use regarding certain themes of and particular time periods, this essay argues that much of the epistemology and philosophy of science in the early twentieth century in a variety of projects (neo-Kantianism, logical empiricism, pragmatism, phenomenology) looked to the then current context of the exact sciences, especially geometry and physics, not merely for its topics but also for its conceptual resources and technical tools. This suggests a more variable project of philosophy of science, a deeper connection between early twentieth-century philosophy of science and its contemporary science, and a more interesting and richer history of philosophy of science than is ordinarily offered. 相似文献
94.
Mailman MD Feolo M Jin Y Kimura M Tryka K Bagoutdinov R Hao L Kiang A Paschall J Phan L Popova N Pretel S Ziyabari L Lee M Shao Y Wang ZY Sirotkin K Ward M Kholodov M Zbicz K Beck J Kimelman M Shevelev S Preuss D Yaschenko E Graeff A Ostell J Sherry ST 《Nature genetics》2007,39(10):1181-1186
The National Center for Biotechnology Information has created the dbGaP public repository for individual-level phenotype, exposure, genotype and sequence data and the associations between them. dbGaP assigns stable, unique identifiers to studies and subsets of information from those studies, including documents, individual phenotypic variables, tables of trait data, sets of genotype data, computed phenotype-genotype associations, and groups of study subjects who have given similar consents for use of their data. 相似文献
95.
Attie AD 《Nature genetics》2007,39(12):1424-1425
96.
Volkman SK Sabeti PC DeCaprio D Neafsey DE Schaffner SF Milner DA Daily JP Sarr O Ndiaye D Ndir O Mboup S Duraisingh MT Lukens A Derr A Stange-Thomann N Waggoner S Onofrio R Ziaugra L Mauceli E Gnerre S Jaffe DB Zainoun J Wiegand RC Birren BW Hartl DL Galagan JE Lander ES Wirth DF 《Nature genetics》2007,39(1):113-119
Genetic variation allows the malaria parasite Plasmodium falciparum to overcome chemotherapeutic agents, vaccines and vector control strategies and remain a leading cause of global morbidity and mortality. Here we describe an initial survey of genetic variation across the P. falciparum genome. We performed extensive sequencing of 16 geographically diverse parasites and identified 46,937 SNPs, demonstrating rich diversity among P. falciparum parasites (pi = 1.16 x 10(-3)) and strong correlation with gene function. We identified multiple regions with signatures of selective sweeps in drug-resistant parasites, including a previously unidentified 160-kb region with extremely low polymorphism in pyrimethamine-resistant parasites. We further characterized 54 worldwide isolates by genotyping SNPs across 20 genomic regions. These data begin to define population structure among African, Asian and American groups and illustrate the degree of linkage disequilibrium, which extends over relatively short distances in African parasites but over longer distances in Asian parasites. We provide an initial map of genetic diversity in P. falciparum and demonstrate its potential utility in identifying genes subject to recent natural selection and in understanding the population genetics of this parasite. 相似文献
97.
98.
DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis 总被引:14,自引:0,他引:14
Lorenz-Depiereux B Bastepe M Benet-Pagès A Amyere M Wagenstaller J Müller-Barth U Badenhoop K Kaiser SM Rittmaster RS Shlossberg AH Olivares JL Loris C Ramos FJ Glorieux F Vikkula M Jüppner H Strom TM 《Nature genetics》2006,38(11):1248-1250
Hypophosphatemia is a genetically heterogeneous disease. Here, we mapped an autosomal recessive form (designated ARHP) to chromosome 4q21 and identified homozygous mutations in DMP1 (dentin matrix protein 1), which encodes a non-collagenous bone matrix protein expressed in osteoblasts and osteocytes. Intact plasma levels of the phosphaturic protein FGF23 were clearly elevated in two of four affected individuals, providing a possible explanation for the phosphaturia and inappropriately normal 1,25(OH)2D levels and suggesting that DMP1 may regulate FGF23 expression. 相似文献
99.
A combination of in vitro and in vivo models with validation in human tumors has identified AXL activation as a new mechanism of acquired resistance to EGFR inhibitors in non-small cell lung cancer. The identification of this mechanism, alongside the current development of specific AXL inhibitors, provides the rationale for further studies that may improve treatment for EGFR inhibitor-resistant patients. 相似文献