全文获取类型
收费全文 | 2370篇 |
免费 | 135篇 |
国内免费 | 1篇 |
出版年
2023年 | 18篇 |
2022年 | 33篇 |
2021年 | 77篇 |
2020年 | 39篇 |
2019年 | 52篇 |
2018年 | 84篇 |
2017年 | 55篇 |
2016年 | 80篇 |
2015年 | 104篇 |
2014年 | 146篇 |
2013年 | 186篇 |
2012年 | 178篇 |
2011年 | 178篇 |
2010年 | 126篇 |
2009年 | 94篇 |
2008年 | 115篇 |
2007年 | 135篇 |
2006年 | 96篇 |
2005年 | 93篇 |
2004年 | 66篇 |
2003年 | 64篇 |
2002年 | 54篇 |
2001年 | 28篇 |
2000年 | 27篇 |
1999年 | 20篇 |
1997年 | 10篇 |
1996年 | 6篇 |
1995年 | 13篇 |
1994年 | 10篇 |
1992年 | 12篇 |
1991年 | 26篇 |
1990年 | 17篇 |
1989年 | 23篇 |
1988年 | 12篇 |
1987年 | 11篇 |
1986年 | 9篇 |
1985年 | 17篇 |
1984年 | 23篇 |
1983年 | 10篇 |
1982年 | 17篇 |
1981年 | 10篇 |
1980年 | 10篇 |
1979年 | 23篇 |
1978年 | 11篇 |
1977年 | 14篇 |
1975年 | 13篇 |
1974年 | 6篇 |
1973年 | 10篇 |
1972年 | 9篇 |
1971年 | 7篇 |
排序方式: 共有2506条查询结果,搜索用时 265 毫秒
71.
72.
Dipankar Ray Shirish Shukla Uday Sankar Allam Abigail Helman Susmita Gurjar Ramanand Linda Tran Michael Bassetti Pranathi Meda Krishnamurthy Matthew Rumschlag Michelle Paulsen Lei Sun Thomas P. Shanley Mats Ljungman Mukesh K. Nyati Ming Zhang Theodore S. Lawrence 《PloS one》2013,8(2)
The efficacy of radiation therapy for lung cancer is limited by radiation-induced lung toxicity (RILT). Although tumor necrosis factor-alpha (TNF-α) signaling plays a critical role in RILT, the molecular regulators of radiation-induced TNF-α production remain unknown. We investigated the role of a major TNF-α regulator, Tristetraprolin (TTP), in radiation-induced TNF-α production by macrophages. For in vitro studies we irradiated (4 Gy) either a mouse lung macrophage cell line, MH-S or macrophages isolated from TTP knockout mice, and studied the effects of radiation on TTP and TNF-α levels. To study the in vivo relevance, mouse lungs were irradiated with a single dose (15 Gy) and assessed at varying times for TTP alterations. Irradiation of MH-S cells caused TTP to undergo an inhibitory phosphorylation at Ser-178 and proteasome-mediated degradation, which resulted in increased TNF-α mRNA stabilization and secretion. Similarly, MH-S cells treated with TTP siRNA or macrophages isolated from ttp (−/−) mice had higher basal levels of TNF-α, which was increased minimally after irradiation. Conversely, cells overexpressing TTP mutants defective in undergoing phosphorylation released significantly lower levels of TNF-α. Inhibition of p38, a known kinase for TTP, by either siRNA or a small molecule inhibitor abrogated radiation-induced TNF-α release by MH-S cells. Lung irradiation induced TTPSer178 phosphorylation and protein degradation and a simultaneous increase in TNF-α production in C57BL/6 mice starting 24 h post-radiation. In conclusion, irradiation of lung macrophages causes TTP inactivation via p38-mediated phosphorylation and proteasome-mediated degradation, leading to TNF-α production. These findings suggest that agents capable of blocking TTP phosphorylation or stabilizing TTP after irradiation could decrease RILT. 相似文献
73.
Objectives
There has been increased interest in the possible role of human cytomegalovirus (HCMV) in carcinogenesis during the last decade. HCMV seroprevalence was enhanced in patients with hepatocellular carcinoma (HCC) but a possible relationship between HCC and HCMV infection remained to be assessed. The aim of this work was to investigate the pro-tumor influence of HCMV on primary human hepatocytes (PHH) and HepG2 cells.Methods
Following infection of PHH and HepG2 cells by two different strains of HCMV, we measured the production of IL-6 in culture supernatants by ELISA and the protein levels of STAT3, pSTAT3, JAK, cyclin D1, survivin, p53, p21, and Mdm2 by western Blotting in infected and uninfected cells. Cell proliferation and transformation were investigated using Ki67Ag expression measurement and soft-agar colony formation assay respectively.Results
Infection of HepG2 cells and PHH by HCMV resulted in the production of IL-6 and the subsequent activation of the IL-6R-JAK-STAT3 pathway. HCMV increased the expression of cyclin D1 and survivin. Cell proliferation was enhanced in HepG2 and PHH infected with HCMV, despite a paradoxical overexpression of p53 and p21. More importantly, we observed the formation of colonies in soft agar seeded with PHH infected with HCMV and when we challenged the HepG2 cultures to form tumorspheres, we found that the HCMV-infected cultures formed 2.5-fold more tumorspheres than uninfected cultures.Conclusion
HCMV activated the IL-6-JAK-STAT3 pathway in PHH and HepG2 cells, favored cellular proliferation, induced PHH transformation and enhanced HepG2 tumorsphere formation. Our observations raise the possibility that HCMV infection might be involved in the genesis of hepatocellular carcinoma. 相似文献74.
Gupta Praveen Kumar Vaswani Shalini Kumar Vinod Roy Debashis Kumar Muneendra Kushwaha Raju Kumar Avinash Shukla Amit 《Biological trace element research》2020,194(2):379-389
Biological Trace Element Research - This study was conducted to investigate the effect of vanadium (V) supplementation on growth, metabolism, antioxidant, and immunological and endocrine variables... 相似文献
75.
Kumar Alok Kalita J. Sinha Rohit A. Singh Gajendra B Anjum Shukla Mukti Tiwari Swasti Dhole T. N. Misra U. K. 《Neurochemical research》2020,45(9):2184-2195
Neurochemical Research - Role of autophagy in Japanese encephalitis viral (JEV) infection is not well known. In the present study, we reported the role of autophagy flux in microglia activation,... 相似文献
76.
Madeleine Scharf Stefan Neef Robert Freund Cornelia Geers-Kn?rr Mirita Franz-Wachtel Almuth Brandis Dorothee Krone Heike Schneider Stephanie Groos Manoj B. Menon Kin-Chow Chang Theresia Kraft Joachim D. Meissner Kenneth R. Boheler Lars S. Maier Matthias Gaestel Renate J. Scheibe 《Molecular and cellular biology》2013,33(13):2586-2602
77.
78.
Anumeha Shukla R. C. Mehrotra Nivedita Mandal Mahesh G. Thakkar 《Historical Biology》2013,25(8):970-977
The Kutch region of western India (Gujarat State) is today arid to semiarid and characterised by mostly ephemeral streams which carry water during the monsoon. The uneven distribution of rainfall and disturbed topography are the result of climate change during the Cenozoic period. Two fossil woods, namely Bauhinium palaeomalabaricum Prakash and Prasad (Fabaceae) and Ebenoxylon indicum Ghosh and Kazmi (Ebenaceae), are described from Kutch in order to provide insights into the palaeovegetation and palaeoclimate. Because the modern representatives of the present and previously described taxa from the same horizon are thermophilic in nature and grow in evergreen to deciduous forests, a warm and humid climate is interpreted. Furthermore, the finding of some mangrove taxa in the assemblage indicates the lagoonal to intertidal environment at the time of deposition. 相似文献
79.
80.
Manoj Cheriyan Chandra Sekhar Pedamallu Kazuo Tori Francine Perler 《The Journal of biological chemistry》2013,288(9):6202-6211
Inteins are naturally occurring intervening sequences that catalyze a protein splicing reaction resulting in intein excision and concatenation of the flanking polypeptides (exteins) with a native peptide bond. Inteins display a diversity of catalytic mechanisms within a highly conserved fold that is shared with hedgehog autoprocessing proteins. The unusual chemistry of inteins has afforded powerful biotechnology tools for controlling enzyme function upon splicing and allowing peptides of different origins to be coupled in a specific, time-defined manner. The extein sequences immediately flanking the intein affect splicing and can be defined as the intein substrate. Because of the enormous potential complexity of all possible flanking sequences, studying intein substrate specificity has been difficult. Therefore, we developed a genetic selection for splicing-dependent kanamycin resistance with no significant bias when six amino acids that immediately flanked the intein insertion site were randomized. We applied this selection to examine the sequence space of residues flanking the Nostoc punctiforme Npu DnaE intein and found that this intein efficiently splices a much wider range of sequences than previously thought, with little N-extein specificity and only two important C-extein positions. The novel selected extein sequences were sufficient to promote splicing in three unrelated proteins, confirming the generalizable nature of the specificity data and defining new potential insertion sites for any target. Kinetic analysis showed splicing rates with the selected exteins that were as fast or faster than the native extein, refuting past assumptions that the naturally selected flanking extein sequences are optimal for splicing. 相似文献