全文获取类型
收费全文 | 2330篇 |
免费 | 157篇 |
国内免费 | 151篇 |
出版年
2024年 | 17篇 |
2023年 | 78篇 |
2022年 | 71篇 |
2021年 | 120篇 |
2020年 | 95篇 |
2019年 | 111篇 |
2018年 | 121篇 |
2017年 | 62篇 |
2016年 | 82篇 |
2015年 | 85篇 |
2014年 | 141篇 |
2013年 | 186篇 |
2012年 | 114篇 |
2011年 | 101篇 |
2010年 | 90篇 |
2009年 | 82篇 |
2008年 | 94篇 |
2007年 | 92篇 |
2006年 | 100篇 |
2005年 | 80篇 |
2004年 | 67篇 |
2003年 | 62篇 |
2002年 | 68篇 |
2001年 | 53篇 |
2000年 | 31篇 |
1999年 | 41篇 |
1998年 | 34篇 |
1997年 | 26篇 |
1996年 | 33篇 |
1995年 | 24篇 |
1994年 | 22篇 |
1993年 | 21篇 |
1992年 | 19篇 |
1991年 | 19篇 |
1990年 | 22篇 |
1989年 | 10篇 |
1988年 | 14篇 |
1987年 | 7篇 |
1986年 | 16篇 |
1985年 | 16篇 |
1984年 | 22篇 |
1983年 | 12篇 |
1982年 | 16篇 |
1981年 | 14篇 |
1980年 | 6篇 |
1979年 | 9篇 |
1978年 | 7篇 |
1977年 | 7篇 |
1976年 | 6篇 |
1975年 | 6篇 |
排序方式: 共有2638条查询结果,搜索用时 15 毫秒
211.
《Trends in plant science》2015,20(9):586-594
Download : Download video (27MB) 相似文献
212.
213.
Virginia Boccardi Neetu Razdan Jessica Kaplunov Jyoti J. Mundra Masayuki Kimura Abraham Aviv Utz Herbig 《Aging cell》2015,14(3):372-381
Disruption of telomere maintenance pathways leads to accelerated entry into cellular senescence, a stable proliferative arrest that promotes aging‐associated disorders in some mammals. The budding yeast CST complex, comprising Cdc13, Stn1, and Ctc1, is critical for telomere replication, length regulation, and end protection. Although mammalian homologues of CST have been identified recently, their role and function for telomere maintenance in normal somatic human cells are still incompletely understood. Here, we characterize the function of human Stn1 in cultured human fibroblasts and demonstrate its critical role in telomere replication, length regulation, and function. In the absence of high telomerase activity, shRNA‐mediated knockdown of hStn1 resulted in aberrant and fragile telomeric structures, stochastic telomere attrition, increased telomere erosion rates, telomere dysfunction, and consequently accelerated entry into cellular senescence. Oxidative stress augmented the defects caused by Stn1 knockdown leading to almost immediate cessation of cell proliferation. In contrast, overexpression of hTERT suppressed some of the defects caused by hStn1 knockdown suggesting that telomerase can partially compensate for hStn1 loss. Our findings reveal a critical role for human Stn1 in telomere length maintenance and function, supporting the model that efficient replication of telomeric repeats is critical for long‐term viability of normal somatic mammalian cells. 相似文献
214.
The natural killer cell dysfunction of aged mice is due to the bone marrow stroma and is not restored by IL‐15/IL‐15Rα treatment
下载免费PDF全文
![点击此处可从《Aging cell》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Immune dysfunctions in the elderly result in increased susceptibility to infectious diseases, cancer, and autoimmune diseases. Natural killer (NK) cells are bone marrow‐derived lymphocytes crucial for host defense against several infections and cancer. We have previously shown that compared to young, aged C57BL/6 mice have decreased numbers of mature NK cells in the blood, spleen, and bone marrow, resulting in susceptibility to mousepox, a lethal disease caused by ectromelia virus. Here, we describe further age‐related defects in NK cells including reduced proliferation in vivo, additional signs of immaturity, and dysregulated expression of activating and inhibitory receptors. Aging also alters the expression of collagen‐binding integrins in conventional NK cells and the frequency and phenotype of liver tissue‐resident NK cells. We additionally show that the defect in NK maturation is the consequence of deficient maturational cues provided by bone marrow stromal cells. Moreover, we demonstrate that in aged mice, treatment with complexes of the cytokine IL‐15 and IL‐15Rα induce massive expansion of the NK cells, but most of these NK cells remain immature and are unable to restore resistance to mousepox. The use of rodent model to understand immunosenescence may help the development of treatments to improve the immune fitness of the aged. Our work with NK cells should contribute toward this goal. 相似文献
215.
216.
Kimura T Hosokawa-Muto J Kamatari YO Kuwata K 《Bioorganic & medicinal chemistry letters》2011,21(5):1502-1507
A series of GN8 derivatives were synthesized from various diamines, carboxylic acid derivatives, and nitrogen nucleophiles, and their antiprion activity was tested in TSE-infected mouse neuronal cells. We found that two ethylenediamine units, hydrophobic substituents on the nitrogen atoms, and the diphenylmethane scaffold were essential structural features responsible for the activity. Seven derivatives bearing substituents at the benzylic position exhibited an improved antiprion activity with the IC50 values of 0.51-0.83 μM. Conformational analysis of model compounds suggested that the introduction of the substituent at the benzylic position restricted the conformational variability of the diphenylmethane unit. 相似文献
217.
缺氧诱导因子-1(HIF-1)和缺氧诱导因子-2(HIF-2)是细胞应对缺氧时关键的转录因子,在生物体生理及病理过程中有重要的作用。HIF由一个α亚基和一个β亚基组成二聚体。在蛋白水平上,HIF的稳定性及转录活性受到多种机制的调控,除为人所熟知的O2/PHDs/pVHL降解途径及FIH-1羟基化作用外,分别针对HIF-1α和HIF-2α的特异性调控机制也相继被报道。从HIF-1α和HIF-2α的蛋白结构、稳定性调控、转录激活功能以及两者在细胞代谢、肿瘤发生中的作用等方面对两者的相似性和差异性进行综述。 相似文献
218.
Bagmi Pattanaik Melissa J. Whitaker Beronda L. Montgomery 《Plant signaling & behavior》2011,6(12):2038-2041
Photosynthetic pigment accumulation and cellular and filament morphology are regulated reversibly by green light (GL) and red light (RL) in the cyanobacterium Fremyella diplosiphon during complementary chromatic adaptation (CCA). The photoreceptor RcaE (regulator of chromatic adaptation), which appears to function as a light-responsive sensor kinase, controls both of these responses. Recent findings indicate that downstream of RcaE, the signaling pathways leading to light-dependent changes in morphology or pigment synthesis and/or accumulation branch, and utilize distinct molecular components. We recently reported that the regulation of the accumulation of the GL-absorbing photosynthetic accessory protein phycoerythrin (PE) and photoregulation of cellular morphology are largely independent, as many mutants with severe PE accumulation defects do not have major disruptions in the regulation of cellular morphology. Furthermore, morphology can be disrupted under GL without impacting GL-dependent PE accumulation. Most recently, however, we determined that the disruption of the cpeR gene, which encodes a protein that is known to function as an activator of PE synthesis under GL, results in disruption of cellular morphology under GL and RL. Thus, apart from RcaE, CpeR is only the second known regulator to impact morphology under both light conditions in F. diplosiphon. 相似文献
219.
In a multicellular system, cellular communication is a must for orchestration and coordination of cellular events. Advent of the latest analytical and imaging tools has allowed us to enhance our understanding of the intercellular communication. An intercellular exchange of proteins or intact membrane patches is a ubiquitous phenomenon, and has been the subject of renewed interest, particularly in the context of immune cells. Recent evidence implicates that intercellular protein transfers, including trogocytosis is an important mechanism of the immune system to modulate immune responses and transferred proteins can also contribute to pathology. It has been demonstrated that intercellular protein transfer can be through the internalization/pathway, dissociation-associated pathway, uptake of exosomes and membrane nanotube formations. Exchange of membrane molecules/antigens between immune cells has been observed for a long time, but the mechanisms and functional consequences of these transfers remain unclear. In this review, we will discuss the important findings concerning intercellular protein transfers, possible mechanisms and highlight their physiological relevance to the immune system, with special reference to T cells such as the stimulatory or suppressive immune responses derived from T cells with acquired dendritic cell membrane molecules. 相似文献
220.
张涛姬振伟钱济先 《现代生物医学进展》2011,11(1):165-168
目前细胞培养通常采用二维平面培养技术,但由于在培养板和培养瓶二维细胞培养并不能完全模拟体内细胞的三维生长环境,因此所得的试验数据与在体情况有偏差。然而细胞支架材料却能为细胞提供一个良好的三维生长环境,更利于细胞粘附、生长和增殖。目前可用于细胞支架材料的来源有天然和人工两大类,现将细胞支架研究进展综述如下。 相似文献