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排序方式: 共有489条查询结果,搜索用时 46 毫秒
391.
Geneviève D Proulle V Isidor B Bellais S Serre V Djouadi F Picard C Vignon-Savoye C Bader-Meunier B Blanche S de Vernejoul MC Legeai-Mallet L Fischer AM Le Merrer M Dreyfus M Gaussem P Munnich A Cormier-Daire V 《Nature genetics》2008,40(3):284-286
Studying consanguineous families with Ghosal hematodiaphyseal dysplasia syndrome (GHDD), a disorder of increased bone density, we identified mutations in TBXAS1, which encodes thromboxane synthase (TXAS). TXAS, an enzyme of the arachidonic acid cascade, produces thromboxane A(2) (TXA(2)). Platelets from subjects with GHDD showed a specific deficit in arachidonic acid-produced aggregation. We also found that TXAS and TXA(2) modulated expression of TNFSF11 and TNFRSF11B (encoding RANKL and osteoprotegerin (OPG), respectively) in primary cultured osteoblasts. 相似文献
392.
Rioux JD Xavier RJ Taylor KD Silverberg MS Goyette P Huett A Green T Kuballa P Barmada MM Datta LW Shugart YY Griffiths AM Targan SR Ippoliti AF Bernard EJ Mei L Nicolae DL Regueiro M Schumm LP Steinhart AH Rotter JI Duerr RH Cho JH Daly MJ Brant SR 《Nature genetics》2007,39(5):596-604
We present a genome-wide association study of ileal Crohn disease and two independent replication studies that identify several new regions of association to Crohn disease. Specifically, in addition to the previously established CARD15 and IL23R associations, we identified strong and significantly replicated associations (combined P < 10(-10)) with an intergenic region on 10q21.1 and a coding variant in ATG16L1, the latter of which was also recently reported by another group. We also report strong associations with independent replication to variation in the genomic regions encoding PHOX2B, NCF4 and a predicted gene on 16q24.1 (FAM92B). Finally, we demonstrate that ATG16L1 is expressed in intestinal epithelial cell lines and that functional knockdown of this gene abrogates autophagy of Salmonella typhimurium. Together, these findings suggest that autophagy and host cell responses to intracellular microbes are involved in the pathogenesis of Crohn disease. 相似文献
393.
Integrity of the blood vessel wall is essential for vascular homeostasis and organ function. A dynamic balance between endothelial cell survival and apoptosis contributes to this integrity during vascular development and pathological angiogenesis. The genetic and molecular mechanisms regulating these processes in vivo are still largely unknown. Here, we show that Birc2 (also known as cIap1) is essential for maintaining endothelial cell survival and blood vessel homeostasis during vascular development. Using a forward-genetic approach, we identified a zebrafish null mutant for birc2, which shows severe hemorrhage and vascular regression due to endothelial cell integrity defects and apoptosis. Using genetic and molecular approaches, we show that Birc2 positively regulates the formation of the TNF receptor complex I in endothelial cells, thereby promoting NF-kappaB activation and maintaining vessel integrity and stabilization. In the absence of Birc2, a caspase-8-dependent apoptotic program takes place that leads to vessel regression. Our findings identify Birc2 and TNF signaling components as critical regulators of vascular integrity and endothelial cell survival, thereby providing an additional target pathway for the control of angiogenesis and blood vessel homeostasis during embryogenesis, regeneration and tumorigenesis. 相似文献
394.
吴雄武 《南京工业大学学报(自然科学版)》2006,28(1)
采用新近提出的迷向周期和方法(IPS),结合自导Lang evin动态模拟,模拟研究9余肽折褶成β簮结构的情况,表明了该结构与NMR观察到的基本一致,而Ewald模拟由于是强烈的镜像相互作用会产生构型偏差,获得致密构型的几率增大,表明IPS方法更适合于周期边界条件的模拟. 相似文献
395.
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397.
The emergence of mutual knowledge is a major cognitive mechanism for the robustness of complex socio-technical systems. It has been extensively studied from an ethnomethodological point of view and empirically reproduced by multi-agent simulations. Whilst such simulations have been used to design real work settings the underlying theoretical grounding for the process is vague. The aim of this paper is to investigate whether the emergence of mutual knowledge (MK) in a group of colocated individuals can be explained as a percolation phenomenon. The followed methodology consists in coupling agent-based simulation with dynamic networks analysis to study information propagation phenomena: After using an agent-based simulation the authors generated and then analyzed its traces as networks where agents met and exchanged knowledge. Deep analysis of the resulting networks clearly shows that the emergence of MK is comparable to a percolation process. The authors specifically focus on how changes at the microscopic level in the proposed agent based simulator affect percolation and robustness. These results therefore provide theoretical basis for the analysis of social organizations. 相似文献
398.
The anonymous set of astronomical tables preserved in Paris, Bibliothèque nationale de France, MS lat. 10262, is the first set of displaced tables to be found in a medieval Latin text. These tables are a reworking of the standard Alfonsine tables and yield the same results. However, the mean motions are defined differently, the presentation of the tables is unprecedented, and some new functions are introduced for computing true planetary longitudes. The absence of any instructions as well as unusual technical terms in the headings make it difficult to appreciate the cleverness that went into the construction of these tables that are extant in a unique copy. In this article we provide a detailed analysis of these tables and their underlying parameters. The displaced tables are typical of a pervasive tendency in Islamic science to provide extensive and elegant numerical tables for the convenience of practitioners. The underlying astronomical theory is neither questioned nor affected. Edward S. Kennedy 相似文献
399.
Peña-Llopis S Vega-Rubín-de-Celis S Liao A Leng N Pavía-Jiménez A Wang S Yamasaki T Zhrebker L Sivanand S Spence P Kinch L Hambuch T Jain S Lotan Y Margulis V Sagalowsky AI Summerour PB Kabbani W Wong SW Grishin N Laurent M Xie XJ Haudenschild CD Ross MT Bentley DR Kapur P Brugarolas J 《Nature genetics》2012,44(7):751-759
The molecular pathogenesis of renal cell carcinoma (RCC) is poorly understood. Whole-genome and exome sequencing followed by innovative tumorgraft analyses (to accurately determine mutant allele ratios) identified several putative two-hit tumor suppressor genes, including BAP1. The BAP1 protein, a nuclear deubiquitinase, is inactivated in 15% of clear cell RCCs. BAP1 cofractionates with and binds to HCF-1 in tumorgrafts. Mutations disrupting the HCF-1 binding motif impair BAP1-mediated suppression of cell proliferation but not deubiquitination of monoubiquitinated histone 2A lysine 119 (H2AK119ub1). BAP1 loss sensitizes RCC cells in vitro to genotoxic stress. Notably, mutations in BAP1 and PBRM1 anticorrelate in tumors (P = 3 × 10(-5)), and combined loss of BAP1 and PBRM1 in a few RCCs was associated with rhabdoid features (q = 0.0007). BAP1 and PBRM1 regulate seemingly different gene expression programs, and BAP1 loss was associated with high tumor grade (q = 0.0005). Our results establish the foundation for an integrated pathological and molecular genetic classification of RCC, paving the way for subtype-specific treatments exploiting genetic vulnerabilities. 相似文献
400.
Mesenchymal stem cells and neural crest stem cells from adult bone marrow: characterization of their surprising similarities and differences 总被引:1,自引:1,他引:0