全文获取类型
收费全文 | 12212篇 |
免费 | 911篇 |
国内免费 | 361篇 |
出版年
2024年 | 19篇 |
2023年 | 90篇 |
2022年 | 246篇 |
2021年 | 385篇 |
2020年 | 290篇 |
2019年 | 351篇 |
2018年 | 406篇 |
2017年 | 317篇 |
2016年 | 424篇 |
2015年 | 683篇 |
2014年 | 795篇 |
2013年 | 867篇 |
2012年 | 1089篇 |
2011年 | 1031篇 |
2010年 | 650篇 |
2009年 | 555篇 |
2008年 | 731篇 |
2007年 | 655篇 |
2006年 | 535篇 |
2005年 | 490篇 |
2004年 | 510篇 |
2003年 | 395篇 |
2002年 | 315篇 |
2001年 | 255篇 |
2000年 | 211篇 |
1999年 | 208篇 |
1998年 | 96篇 |
1997年 | 65篇 |
1996年 | 56篇 |
1995年 | 63篇 |
1994年 | 59篇 |
1993年 | 44篇 |
1992年 | 81篇 |
1991年 | 75篇 |
1990年 | 55篇 |
1989年 | 49篇 |
1988年 | 35篇 |
1987年 | 24篇 |
1986年 | 27篇 |
1985年 | 25篇 |
1983年 | 17篇 |
1982年 | 13篇 |
1980年 | 20篇 |
1979年 | 19篇 |
1978年 | 12篇 |
1977年 | 18篇 |
1976年 | 12篇 |
1975年 | 15篇 |
1974年 | 16篇 |
1970年 | 12篇 |
排序方式: 共有10000条查询结果,搜索用时 171 毫秒
211.
212.
Soo Youn Kim Zheng-Yi Xu Kyungyoung Song Dae Heon Kim Hyangju Kang Ilka Reichardt Eun Ju Sohn Ji?í Friml Gerd Juergens Inhwan Hwang 《The Plant cell》2013,25(8):2970-2985
Fertilization in flowering plants requires the temporal and spatial coordination of many developmental processes, including pollen production, anther dehiscence, ovule production, and pollen tube elongation. However, it remains elusive as to how this coordination occurs during reproduction. Here, we present evidence that endocytosis, involving heterotetrameric adaptor protein complex 2 (AP-2), plays a crucial role in fertilization. An Arabidopsis thaliana mutant ap2m displays multiple defects in pollen production and viability, as well as elongation of staminal filaments and pollen tubes, all of which are pivotal processes needed for fertilization. Of these abnormalities, the defects in elongation of staminal filaments and pollen tubes were partially rescued by exogenous auxin. Moreover, DR5rev:GFP (for green fluorescent protein) expression was greatly reduced in filaments and anthers in ap2m mutant plants. At the cellular level, ap2m mutants displayed defects in both endocytosis of N-(3-triethylammonium-propyl)-4-(4-diethylaminophenylhexatrienyl) pyridinium dibromide, a lypophilic dye used as an endocytosis marker, and polar localization of auxin-efflux carrier PIN FORMED2 (PIN2) in the stamen filaments. Moreover, these defects were phenocopied by treatment with Tyrphostin A23, an inhibitor of endocytosis. Based on these results, we propose that AP-2–dependent endocytosis plays a crucial role in coordinating the multiple developmental aspects of male reproductive organs by modulating cellular auxin level through the regulation of the amount and polarity of PINs. 相似文献
213.
214.
Abigail R. Green Mark S. Nissen G.N. Mohan Kumar N. Richard Knowles ChulHee Kang 《The Plant cell》2013,25(12):5043-5052
Potato (Solanum tuberosum) multicystatin (PMC) is a unique cystatin composed of eight repeating units, each capable of inhibiting cysteine proteases. PMC is a composite of several cystatins linked by trypsin-sensitive (serine protease) domains and undergoes transitions between soluble and crystalline forms. However, the significance and the regulatory mechanism or mechanisms governing these transitions are not clearly established. Here, we report the 2.2-Å crystal structure of the trypsin-resistant PMC core consisting of the fifth, sixth, and seventh domains. The observed interdomain interaction explains PMC’s resistance to trypsin and pH-dependent solubility/aggregation. Under acidic pH, weakening of the interdomain interactions exposes individual domains, resulting in not only depolymerization of the crystalline form but also exposure of cystatin domains for inhibition of cysteine proteases. This in turn allows serine protease–mediated fragmentation of PMC, producing ∼10-kD domains with intact inhibitory capacity and faster diffusion, thus enhancing PMC’s inhibitory ability toward cysteine proteases. The crystal structure, light-scattering experiments, isothermal titration calorimetry, and site-directed mutagenesis confirmed the critical role of pH and N-terminal residues in these dynamic transitions between monomer/polymer of PMC. Our data support a notion that the pH-dependent structural regulation of PMC has defense-related implications in tuber physiology via its ability to regulate protein catabolism. 相似文献
215.
Min Sun Shin Jin Soo Lee Naeun Lee Won-Woo Lee Sang Hyun Kim Insoo Kang 《Cytokine》2013,61(2):485-490
We investigated whether healthy young (age ? 40) and elderly (age ? 65) people infected with cytomegalovirus (CMV) had similar levels of CD8+ T cell cytokine production and proliferation in response to an immunodominant CMV pp65 peptide pool given the role of CD8+ T cells in controlling viral infection and the association of CMV with immunosenescence. Plus, we determined the effects of aging and CMV-infectious status on plasma levels of IL-27, an innate immune cytokine with pro- and anti-inflammatory properties, as well as on its relationship to IFN-γ in that IL-27 can promote the production of IFN-γ. The results of our study show that young and elderly people had similar levels of CD8+ T cell proliferation, and IFN-γ and TNF-α production in response to CMV pp65 peptides. Plasma levels of IL-27 were similar between the two groups although CMV-infected young and elderly people had a trend toward increased levels of IL-27. Regardless of aging and CMV-infectious status, plasma levels of IL-27 correlated highly with plasma levels of IFN-γ. These findings suggest the maintenance of CMV pp65-specific CD8+ T cell proliferation and cytokine production with aging as well as the sustaining of circulatory IL-27 levels and its biological link to IFN-γ in young and elderly people irrespective of CMV infection. 相似文献
216.
Hee Kyoung Kang Jung Han Suh Jung Jin Lee Sun Hee Yoon Jin Won Hyun Seong Won Choi 《Free radical research》2013,47(7):773-779
The present study was undertaken to examine the effect of l-ascorbic acid (LAA) on the growth of HL-60 promyelocytic leukemia cells, besides induction of apoptosis. LAA (≥10-4?M) was found to markedly inhibit the proliferation of HL-60 in liquid culture and clonogenicity in semisolid culture. Moreover, LAA-treated HL-60 showed activity to produce chemiluminescence and expressed CD 66b cell surface antigens, indicating that LAA induces the differentiation of HL-60 mainly into granulocytes. The results are supported by morphological changes of LAA-treated HL-60 into segmented neutrophils. Therefore, the inhibitory effect of LAA on the growth of HL-60 cells seems to arise from the induction of differentiation. To assess the potential role of LAA, cells were exposed to oxygen radical scavengers in the absence or presence of LAA. Catalase abolished and superoxide dismutase promoted LAA-induced differentiation of HL-60. Thus, H2O2 produced as a result of LAA treatment seems to play a major role in induction of HL-60 differentiation. 相似文献
217.
Jin Sil Chung Seung Baek Lee Seon Ho Park Sung Tae Kang Ah Ram Na Tong-Shin Chang 《Free radical research》2013,47(8):729-737
Reactive oxygen species (ROS) steady-state levels are required for entry into the S phase of the cell cycle in normal cells, as well as in tumour cells. However, the contribution of mitochondrial ROS to normal cell proliferation has not been well investigated thus far. A previous report showed that Romo1 was responsible for the high ROS levels in tumour cells. Here, we show that endogenous ROS generated by Romo1 are indispensable for cell cycle transition from G1 to S phase in normal WI-38 human lung fibroblasts. The ROS level in these cells was down-regulated by Romo1 knockdown, resulting in cell cycle arrest in the G1 phase. This arrest was associated with an increase in the level of p27Kip1. These results demonstrate that mitochondrial ROS generated by Romo1 expression is required for normal cell proliferation and it is suggested that Romo1 plays an important role in redox signalling during normal cell proliferation. 相似文献
218.
Heat shock may increase oxidative stress due to increased production of reactive oxygen species and/or the promotion of cellular oxidation events. Mitochondrial NADP+-dependent isocitrate dehydrogenase (IDPm) produces NADPH, an essential reducing equivalent for the antioxidant system. The protective role of IDPm against heat shock in HEK293 cells, an embryonic kidney cell line, was investigated in control and cells transfected with the cDNA for IDPm, where IDPm activity was 6–7 fold higher than that in the control cells carrying the vector alone. Upon exposure to heat shock, the viability was lower and the protein oxidation, lipid peroxidation and oxidative DNA damage were higher in control cells as compared to HEK293 cells in which IDPm was over-expressed. We also observed the significant difference in the cellular redox status reflected by the endogenous production of reactive oxygen species, NADPH pool and GSH recycling between two cells. The results suggest that IDPm plays an important role as an antioxidant defense enzyme in cellular defense against heat shock through the removal of reactive oxygen species. 相似文献
219.
Eun Sil Kang Gil Hyeong Kim Im Sun Woo Hyo Jung Kim So Young Eun Sun Ah Ham 《Free radical research》2013,47(11-12):930-938
Aldose reductase (AR) is abundantly expressed in a variety of cell lineages and has been implicated in the cellular response against oxidative stress. However, the exact functional role of AR against oxidative stress remains relatively unclear. This study investigated the role of AR in acrolein- or hydrogen peroxide-induced apoptosis using the J774.A.1 macrophage cell line. Ablation of AR with a small interference RNA or inhibition of AR activity significantly enhanced the acrolein- or hydrogen peroxide-induced generation of reactive oxygen species and aldehydes, leading to increased apoptotic cell death. Blockade of AR activity in J774A.1 cells markedly augmented the acrolein- or hydrogen peroxide-induced translocation of Bax to mitochondria along with reduced Bcl-2 and increased release of cytochrome c from the mitochodria. Taken together, these findings indicate that AR plays an important role in the cellular response against oxidative stress, by sequestering the reactive molecules generated in cells exposed to toxic substances. 相似文献