全文获取类型
收费全文 | 44篇 |
免费 | 0篇 |
专业分类
理论与方法论 | 1篇 |
现状及发展 | 10篇 |
研究方法 | 3篇 |
综合类 | 30篇 |
出版年
2019年 | 1篇 |
2018年 | 1篇 |
2014年 | 1篇 |
2013年 | 1篇 |
2012年 | 5篇 |
2011年 | 4篇 |
2010年 | 1篇 |
2008年 | 1篇 |
2007年 | 3篇 |
2005年 | 3篇 |
2004年 | 1篇 |
2003年 | 2篇 |
2002年 | 3篇 |
2001年 | 3篇 |
2000年 | 2篇 |
1999年 | 1篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1986年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1971年 | 2篇 |
1970年 | 1篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有44条查询结果,搜索用时 15 毫秒
1.
Telomere dysfunction may result in chromosomal abnormalities, DNA damage responses, and even cancer. Early studies in lower organisms have helped to establish the crucial role of telomerase and telomeric proteins in maintaining telomere length and protecting telomere ends. In Oxytricha nova, telomere G-overhangs are protected by the TEBP-alpha/beta heterodimer. Human telomeres contain duplex telomeric repeats with 3' single-stranded G-overhangs, and may fold into a t-loop structure that helps to shield them from being recognized as DNA breaks. Additionally, the TEBP-alpha homologue, POT1, which binds telomeric single-stranded DNA (ssDNA), associates with multiple telomeric proteins (for example, TPP1, TIN2, TRF1, TRF2 and RAP1) to form the six-protein telosome/shelterin and other subcomplexes. These telomeric protein complexes in turn interact with diverse pathways to form the telomere interactome for telomere maintenance. However, the mechanisms by which the POT1-containing telosome communicates with telomerase to regulate telomeres remain to be elucidated. Here we demonstrate that TPP1 is a putative mammalian homologue of TEBP-beta and contains a predicted amino-terminal oligonucleotide/oligosaccharide binding (OB) fold. TPP1-POT1 association enhanced POT1 affinity for telomeric ssDNA. In addition, the TPP1 OB fold, as well as POT1-TPP1 binding, seemed critical for POT1-mediated telomere-length control and telomere-end protection in human cells. Disruption of POT1-TPP1 interaction by dominant negative TPP1 expression or RNA interference (RNAi) resulted in telomere-length alteration and DNA damage responses. Furthermore, we offer evidence that TPP1 associates with the telomerase in a TPP1-OB-fold-dependent manner, providing a physical link between telomerase and the telosome/shelterin complex. Our findings highlight the critical role of TPP1 in telomere maintenance, and support a yin-yang model in which TPP1 and POT1 function as a unit to protect human telomeres, by both positively and negatively regulating telomerase access to telomere DNA. 相似文献
2.
3.
4.
Tat-specific cytotoxic T lymphocytes select for SIV escape variants during resolution of primary viraemia 总被引:55,自引:0,他引:55
Allen TM O'Connor DH Jing P Dzuris JL Mothé BR Vogel TU Dunphy E Liebl ME Emerson C Wilson N Kunstman KJ Wang X Allison DB Hughes AL Desrosiers RC Altman JD Wolinsky SM Sette A Watkins DI 《Nature》2000,407(6802):386-390
Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections are characterized by early peaks of viraemia that decline as strong cellular immune responses develop. Although it has been shown that virus-specific CD8-positive cytotoxic T lymphocytes (CTLs) exert selective pressure during HIV and SIV infection, the data have been controversial. Here we show that Tat-specific CD8-positive T-lymphocyte responses select for new viral escape variants during the acute phase of infection. We sequenced the entire virus immediately after the acute phase, and found that amino-acid replacements accumulated primarily in Tat CTL epitopes. This implies that Tat-specific CTLs may be significantly involved in controlling wild-type virus replication, and suggests that responses against viral proteins that are expressed early during the viral life cycle might be attractive targets for HIV vaccine development. 相似文献
5.
6.
Birds are unique among living vertebrates in possessing pneumaticity of the postcranial skeleton, with invasion of bone by the pulmonary air-sac system. The avian respiratory system includes high-compliance air sacs that ventilate a dorsally fixed, non-expanding parabronchial lung. Caudally positioned abdominal and thoracic air sacs are critical components of the avian aspiration pump, facilitating flow-through ventilation of the lung and near-constant airflow during both inspiration and expiration, highlighting a design optimized for efficient gas exchange. Postcranial skeletal pneumaticity has also been reported in numerous extinct archosaurs including non-avian theropod dinosaurs and Archaeopteryx. However, the relationship between osseous pneumaticity and the evolution of the avian respiratory apparatus has long remained ambiguous. Here we report, on the basis of a comparative analysis of region-specific pneumaticity with extant birds, evidence for cervical and abdominal air-sac systems in non-avian theropods, along with thoracic skeletal prerequisites of an avian-style aspiration pump. The early acquisition of this system among theropods is demonstrated by examination of an exceptional new specimen of Majungatholus atopus, documenting these features in a taxon only distantly related to birds. Taken together, these specializations imply the existence of the basic avian pulmonary Bauplan in basal neotheropods, indicating that flow-through ventilation of the lung is not restricted to birds but is probably a general theropod characteristic. 相似文献
7.
8.
iASPP oncoprotein is a key inhibitor of p53 conserved from worm to human 总被引:39,自引:0,他引:39
Bergamaschi D Samuels Y O'Neil NJ Trigiante G Crook T Hsieh JK O'Connor DJ Zhong S Campargue I Tomlinson ML Kuwabara PE Lu X 《Nature genetics》2003,33(2):162-167
We have previously shown that ASPP1 and ASPP2 are specific activators of p53; one mechanism by which wild-type p53 is tolerated in human breast carcinomas is through loss of ASPP activity. We have further shown that 53BP2, which corresponds to a C-terminal fragment of ASPP2, acts as a dominant negative inhibitor of p53 (ref. 1). Hence, an inhibitory form of ASPP resembling 53BP2 could allow cells to bypass the tumor-suppressor functions of p53 and the ASPP proteins. Here, we characterize such a protein, iASPP (inhibitory member of the ASPP family), encoded by PPP1R13L in humans and ape-1 in Caenorhabditis elegans. iASPP is an evolutionarily conserved inhibitor of p53; inhibition of iASPP by RNA-mediated interference or antisense RNA in C. elegans or human cells, respectively, induces p53-dependent apoptosis. Moreover, iASPP is an oncoprotein that cooperates with Ras, E1A and E7, but not mutant p53, to transform cells in vitro. Increased expression of iASPP also confers resistance to ultraviolet radiation and to cisplatin-induced apoptosis. iASPP expression is upregulated in human breast carcinomas expressing wild-type p53 and normal levels of ASPP. Inhibition of iASPP could provide an important new strategy for treating tumors expressing wild-type p53. 相似文献
9.
Halogenation, which was once considered a rare occurrence in nature, has now been observed in many natural product biosynthetic pathways. However, only a small fraction of halogenated compounds have been isolated from terrestrial plants. Given the impact that halogenation can have on the biological activity of natural products, we reasoned that the introduction of halides into medicinal plant metabolism would provide the opportunity to rationally bioengineer a broad variety of novel plant products with altered, and perhaps improved, pharmacological properties. Here we report that chlorination biosynthetic machinery from soil bacteria can be successfully introduced into the medicinal plant Catharanthus roseus (Madagascar periwinkle). These prokaryotic halogenases function within the context of the plant cell to generate chlorinated tryptophan, which is then shuttled into monoterpene indole alkaloid metabolism to yield chlorinated alkaloids. A new functional group-a halide-is thereby introduced into the complex metabolism of C. roseus, and is incorporated in a predictable and regioselective manner onto the plant alkaloid products. Medicinal plants, despite their genetic and developmental complexity, therefore seem to be a viable platform for synthetic biology efforts. 相似文献
10.
Huber D Gutnisky DA Peron S O'Connor DH Wiegert JS Tian L Oertner TG Looger LL Svoboda K 《Nature》2012,484(7395):473-478
The mechanisms linking sensation and action during learning are poorly understood. Layer 2/3 neurons in the motor cortex might participate in sensorimotor integration and learning; they receive input from sensory cortex and excite deep layer neurons, which control movement. Here we imaged activity in the same set of layer 2/3 neurons in the motor cortex over weeks, while mice learned to detect objects with their whiskers and report detection with licking. Spatially intermingled neurons represented sensory (touch) and motor behaviours (whisker movements and licking). With learning, the population-level representation of task-related licking strengthened. In trained mice, population-level representations were redundant and stable, despite dynamism of single-neuron representations. The activity of a subpopulation of neurons was consistent with touch driving licking behaviour. Our results suggest that ensembles of motor cortex neurons couple sensory input to multiple, related motor programs during learning. 相似文献