全文获取类型
收费全文 | 86篇 |
免费 | 0篇 |
专业分类
系统科学 | 4篇 |
理论与方法论 | 3篇 |
现状及发展 | 25篇 |
研究方法 | 13篇 |
综合类 | 41篇 |
出版年
2020年 | 2篇 |
2018年 | 1篇 |
2016年 | 1篇 |
2015年 | 1篇 |
2014年 | 3篇 |
2012年 | 9篇 |
2011年 | 8篇 |
2010年 | 3篇 |
2008年 | 3篇 |
2007年 | 3篇 |
2006年 | 11篇 |
2005年 | 9篇 |
2004年 | 4篇 |
2003年 | 5篇 |
2002年 | 6篇 |
2001年 | 1篇 |
2000年 | 1篇 |
1996年 | 1篇 |
1988年 | 1篇 |
1986年 | 1篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1972年 | 3篇 |
1969年 | 2篇 |
1966年 | 2篇 |
1958年 | 1篇 |
排序方式: 共有86条查询结果,搜索用时 218 毫秒
41.
42.
Pérez-Mancera PA Rust AG van der Weyden L Kristiansen G Li A Sarver AL Silverstein KA Grützmann R Aust D Rümmele P Knösel T Herd C Stemple DL Kettleborough R Brosnan JA Li A Morgan R Knight S Yu J Stegeman S Collier LS ten Hoeve JJ de Ridder J Klein AP Goggins M Hruban RH Chang DK Biankin AV Grimmond SM;Australian Pancreatic Cancer Genome Initiative Wessels LF Wood SA Iacobuzio-Donahue CA Pilarsky C Largaespada DA Adams DJ Tuveson DA 《Nature》2012,486(7402):266-270
Pancreatic ductal adenocarcinoma (PDA) remains a lethal malignancy despite much progress concerning its molecular characterization. PDA tumours harbour four signature somatic mutations in addition to numerous lower frequency genetic events of uncertain significance. Here we use Sleeping Beauty (SB) transposon-mediated insertional mutagenesis in a mouse model of pancreatic ductal preneoplasia to identify genes that cooperate with oncogenic Kras(G12D) to accelerate tumorigenesis and promote progression. Our screen revealed new candidate genes for PDA and confirmed the importance of many genes and pathways previously implicated in human PDA. The most commonly mutated gene was the X-linked deubiquitinase Usp9x, which was inactivated in over 50% of the tumours. Although previous work had attributed a pro-survival role to USP9X in human neoplasia, we found instead that loss of Usp9x enhances transformation and protects pancreatic cancer cells from anoikis. Clinically, low USP9X protein and messenger RNA expression in PDA correlates with poor survival after surgery, and USP9X levels are inversely associated with metastatic burden in advanced disease. Furthermore, chromatin modulation with trichostatin A or 5-aza-2'-deoxycytidine elevates USP9X expression in human PDA cell lines, indicating a clinical approach for certain patients. The conditional deletion of Usp9x cooperated with Kras(G12D) to accelerate pancreatic tumorigenesis in mice, validating their genetic interaction. We propose that USP9X is a major tumour suppressor gene with prognostic and therapeutic relevance in PDA. 相似文献
43.
44.
Domire JS Green JA Lee KG Johnson AD Askwith CC Mykytyn K 《Cellular and molecular life sciences : CMLS》2011,68(17):2951-2960
Primary cilia are nearly ubiquitous cellular appendages that provide important sensory and signaling functions. Ciliary dysfunction
underlies numerous human diseases, collectively termed ciliopathies. Primary cilia have distinct functions on different cell
types and these functions are defined by the signaling proteins that localize to the ciliary membrane. Neurons throughout
the mammalian brain possess primary cilia upon which certain G protein-coupled receptors localize. Yet, the precise signaling
proteins present on the vast majority of neuronal cilia are unknown. Here, we report that dopamine receptor 1 (D1) localizes
to cilia on mouse central neurons, thereby implicating neuronal cilia in dopamine signaling. Interestingly, ciliary localization
of D1 is dynamic, and the receptor rapidly translocates to and from cilia in response to environmental cues. Notably, the
translocation of D1 from cilia requires proteins mutated in the ciliopathy Bardet-Biedl syndrome (BBS), and we find that one
of the BBS proteins, Bbs5, specifically interacts with D1. 相似文献
45.
Leung JY Bennett WR Herbert RP West AK Lee PR Wake H Fields RD Chuah MI Chung RS 《Cellular and molecular life sciences : CMLS》2012,69(5):809-817
Prior studies have reported that metallothionein I/II (MT) promote regenerative axonal sprouting and neurite elongation of
a variety of central nervous system neurons after injury. In this study, we evaluated whether MT is capable of modulating
regenerative axon outgrowth of neurons from the peripheral nervous system. The effect of MT was firstly investigated in dorsal
root ganglion (DRG) explants, where axons were scratch-injured in the presence or absence of exogenous MT. The application
of MT led to a significant increase in regenerative sprouting of neurons 16 h after injury. We show that the pro-regenerative
effect of MT involves an interaction with the low-density lipoprotein receptor megalin, which could be blocked using the competitive
antagonist RAP. Pre-treatment with the mitogen-activated protein kinase (MAPK) inhibitor PD98059 also completely abrogated
the effect of exogenous MT in promoting axonal outgrowth. Interestingly, we only observed megalin expression in neuronal soma
and not axons in the DRG explants. To investigate this matter, an in vitro injury model was established using Campenot chambers,
which allowed the application of MT selectively into either the axonal or cell body compartments after scratch injury was
performed to axons. At 16 h after injury, regenerating axons were significantly longer only when exogenous MT was applied
solely to the soma compartment, in accordance with the localized expression of megalin in neuronal cell bodies. This study
provides a clear indication that MT promotes axonal regeneration of DRG neurons, via a megalin- and MAPK-dependent mechanism. 相似文献
46.
47.
48.
49.
50.
Landscape of transcription in human cells 总被引:3,自引:0,他引:3
S Djebali CA Davis A Merkel A Dobin T Lassmann A Mortazavi A Tanzer J Lagarde W Lin F Schlesinger C Xue GK Marinov J Khatun BA Williams C Zaleski J Rozowsky M Röder F Kokocinski RF Abdelhamid T Alioto I Antoshechkin MT Baer NS Bar P Batut K Bell I Bell S Chakrabortty X Chen J Chrast J Curado T Derrien J Drenkow E Dumais J Dumais R Duttagupta E Falconnet M Fastuca K Fejes-Toth P Ferreira S Foissac MJ Fullwood H Gao D Gonzalez A Gordon H Gunawardena C Howald S Jha R Johnson P Kapranov B King 《Nature》2012,489(7414):101-108
Eukaryotic cells make many types of primary and processed RNAs that are found either in specific subcellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic subcellular localizations are also poorly understood. Because RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell's regulatory capabilities are focused on its synthesis, processing, transport, modification and translation, the generation of such a catalogue is crucial for understanding genome function. Here we report evidence that three-quarters of the human genome is capable of being transcribed, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs. These observations, taken together, prompt a redefinition of the concept of a gene. 相似文献