全文获取类型
收费全文 | 3091篇 |
免费 | 137篇 |
国内免费 | 1篇 |
专业分类
3229篇 |
出版年
2023年 | 33篇 |
2022年 | 57篇 |
2021年 | 79篇 |
2020年 | 61篇 |
2019年 | 62篇 |
2018年 | 96篇 |
2017年 | 66篇 |
2016年 | 116篇 |
2015年 | 135篇 |
2014年 | 150篇 |
2013年 | 231篇 |
2012年 | 266篇 |
2011年 | 227篇 |
2010年 | 155篇 |
2009年 | 138篇 |
2008年 | 160篇 |
2007年 | 146篇 |
2006年 | 129篇 |
2005年 | 98篇 |
2004年 | 93篇 |
2003年 | 100篇 |
2002年 | 56篇 |
2001年 | 48篇 |
2000年 | 37篇 |
1999年 | 27篇 |
1998年 | 20篇 |
1997年 | 17篇 |
1996年 | 19篇 |
1995年 | 13篇 |
1994年 | 10篇 |
1992年 | 26篇 |
1991年 | 19篇 |
1990年 | 23篇 |
1989年 | 18篇 |
1988年 | 24篇 |
1987年 | 18篇 |
1986年 | 22篇 |
1985年 | 23篇 |
1984年 | 19篇 |
1983年 | 24篇 |
1982年 | 12篇 |
1981年 | 13篇 |
1979年 | 18篇 |
1978年 | 9篇 |
1977年 | 12篇 |
1974年 | 12篇 |
1973年 | 7篇 |
1972年 | 18篇 |
1971年 | 12篇 |
1969年 | 10篇 |
排序方式: 共有3229条查询结果,搜索用时 15 毫秒
41.
42.
43.
Targeting of the c-Abl tyrosine kinase to mitochondria in endoplasmic reticulum stress-induced apoptosis 总被引:14,自引:0,他引:14 下载免费PDF全文
Ito Y Pandey P Mishra N Kumar S Narula N Kharbanda S Saxena S Kufe D 《Molecular and cellular biology》2001,21(18):6233-6242
The ubiquitously expressed c-Abl tyrosine kinase localizes to the nucleus and cytoplasm. Using confocal microscopy, we demonstrated that c-Abl colocalizes with the endoplasmic reticulum (ER)-associated protein grp78. Expression of c-Abl in the ER was confirmed by immunoelectron microscopy. Subcellular fractionation studies further indicate that over 20% of cellular c-Abl is detectable in the ER. The results also demonstrate that induction of ER stress with calcium ionophore A23187, brefeldin A, or tunicamycin is associated with translocation of ER-associated c-Abl to mitochondria. In concert with targeting of c-Abl to mitochondria, cytochrome c is released in the response to ER stress by a c-Abl-dependent mechanism, and ER stress-induced apoptosis is attenuated in c-Abl-deficient cells. These findings indicate that c-Abl is involved in signaling from the ER to mitochondria and thereby the apoptotic response to ER stress. 相似文献
44.
Tim Ammon ;Shravan Kumar Mishra ;Kaja Kowalska ;Grzegorz M. Popowicz ;Tad A. Holak ;Stefan Jentsch 《分子细胞生物学报》2014,(4):312-323
Different from canonical ubiquitin-like proteins, Hub1 does not form covalent conjugates with substrates but binds proteins noncovalently. In Socchoromyces cerevisioe, Hub1 associates with spUceosomes and mediates alternative splicing of SRCI, without affecting pre-mRNA splicing generaity. Human Hub1 is highty similar to its yeast homotog, but its cellular function remains largely unexplored. Here, we show that human Hub1 binds to the spliceosomal protein Snu66 as in yeast; however, unlike its 5. cerevisioe homolos, human Hub1 is essential for viability. Prolonged in vivo depletion of human Hub1 leads to various cellular defects, including splicing speckle abnormalities, partial nuclear retention of mRNAs, mitotic catastrophe, and consequently cell death by apoptosis. Early consequences of Hub1 depletion are severe splicing defects, however, only for specific splice sites leading to exon skipping and intron retention. Thus, the ubiquitin-iike protein Hub1 is not a canonlcal spliceosomal factor needed generally for splicing, but rather a modulator of spliceosome performance and facilitator of alternative splicing. 相似文献
45.
Co-degradation of resorcinol and catechol was studied in a catechol acclimated up flow anaerobic sludge blanket (UASB) reactor. Synthetic binary aqueous solution having a total concentration of 1000 mg/L with the resorcinol/catechol (R/C) ratio of 1/19, 1/9, 3/17, 1/4, 1/3, 3/7, 2/3 and then 1/3 was fed at various time intervals to the UASB reactor with a fixed organic loading rate of 5.7 kg COD/m(3) d and hydraulic retention time of 8h. The reactor was operated over a period of 145 days after its acclimation with catechol bearing synthetic wastewater at a constant feed rate of 1.2 L/h. When the resorcinol concentration was increased to have a R/C ratio of 1/4, the COD removal efficiency and the biogas production increased to the maximum levels. Pseudo steady state condition for COD removal was achieved at each of the stepped-up loading condition. An increase in the R/C ratio above 1/4 in the binary feed solution led to a decrease in the COD removal efficiency and the biogas production rate. 相似文献
46.
Garcia BA Hake SB Diaz RL Kauer M Morris SA Recht J Shabanowitz J Mishra N Strahl BD Allis CD Hunt DF 《The Journal of biological chemistry》2007,282(10):7641-7655
Post-translational modifications (PTMs) of histones play an important role in many cellular processes, notably gene regulation. Using a combination of mass spectrometric and immunobiochemical approaches, we show that the PTM profile of histone H3 differs significantly among the various model organisms examined. Unicellular eukaryotes, such as Saccharomyces cerevisiae (yeast) and Tetrahymena thermophila (Tet), for example, contain more activation than silencing marks as compared with mammalian cells (mouse and human), which are generally enriched in PTMs more often associated with gene silencing. Close examination reveals that many of the better-known modified lysines (Lys) can be either methylated or acetylated and that the overall modification patterns become more complex from unicellular eukaryotes to mammals. Additionally, novel species-specific H3 PTMs from wild-type asynchronously grown cells are also detected by mass spectrometry. Our results suggest that some PTMs are more conserved than previously thought, including H3K9me1 and H4K20me2 in yeast and H3K27me1, -me2, and -me3 in Tet. On histone H4, methylation at Lys-20 showed a similar pattern as H3 methylation at Lys-9, with mammals containing more methylation than the unicellular organisms. Additionally, modification profiles of H4 acetylation were very similar among the organisms examined. 相似文献
47.
Surendra K. Gond Ashish Mishra Vijay K. Sharma Satish K. Verma Jitendra Kumar Ravindra N. Kharwar Anuj Kumar 《Mycoscience》2012,53(2):113-121
Endophytic fungi from Nyctanthes arbor-tristis were isolated and evaluated for their antimicrobial activity. A total of 19 endophytic fungi were isolated from 400 segments
of healthy leaf and stem tissues of N. arbor-tristis. Eighteen endophytic fungi were obtained from leaf, while only ten from stem. Alternaria alternata had the highest colonization frequency (15.0%) in leaf, whereas Cladosporium cladosporioides ranked first in stem with a colonization frequency of 12%. The diversity and species richness were found higher in leaf tissues
than in stem. The similarity indices between leaf and stem were 0.473 for Jaccard’s and 0.642 for the Sorenson index, respectively.
Of 16, 12 (75%) endophytic fungal extracts showed antibacterial activity against either one or more pathogenic bacteria. The
endophytic Nigrospora oryzae showed maximum inhibition against Shigella sp. and Pseudomonas aeruginosa. The leaf endophytes Colletotrichum dematium and Chaetomium globosum exhibited a broad range of anibacterial activity and were active against Shigella flexnii, Shigella boydii, Salmonella enteritidis, Salmonella paratyphi, and P. aeruginosa. Nine out of 16 (56.25%) endophytic fungi exhibited antifungal activity to one or more fungal pathogens. Colletotrichum dematium inhibited 55.87% of the radial growth of the phytopathogen Curvularia lunata. The antimicrobial activity of these endophytic microorganisms could be exploited in the biotechnological, medicinal, and
agricultural industries. 相似文献
48.
49.
Syed Mohsin Waheed Arnab Ghosh Ritu Chakravarti Ashis Biswas Mohammad Mahfuzul Haque Koustubh Panda Dennis J. Stuehr 《Free radical biology & medicine》2010,48(11):1548-1558
Although the insertion of heme into proteins enables their function in bioenergetics, metabolism, and signaling, the mechanisms and regulation of this process are not fully understood. We developed a means to study cellular heme insertion into apo-protein targets over a 3-h period and then investigated how nitric oxide (NO) released from a chemical donor (NOC-18) might influence heme (protoporphyrin IX) insertion into seven targets that present a range of protein structures, heme ligation states, and functions (three NO synthases, two cytochrome P450's, catalase, and hemoglobin). NO blocked cellular heme insertion into all seven apo-protein targets. The inhibition occurred at relatively low (nM/min) fluxes of NO, was reversible, and did not involve changes in intracellular heme levels, activation of guanylate cyclase, or inhibition of mitochondrial ATP production. These aspects and the range of protein targets suggest that NO can act as a global inhibitor of heme insertion, possibly by inhibiting a common step in the process. 相似文献
50.
Vikas Kumar Bhari Durgesh Kumar Surendra Kumar Rajeev Mishra 《Biochemistry and Biophysics Reports》2020
The recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has impacted the world severely. The binding of the SARS-CoV-2 virus to the angiotensin-converting enzyme 2 (ACE2) and its intake by the host cell is a necessary step for infection. ACE2 has garnered widespread therapeutic possibility as it is entry/interactive point for SARS-CoV-2, responsible for coronavirus disease 2019 (COVID-19) pandemic and providing a critical regulator for immune modulation in various disease. Patients with suffering from cancer always being on the verge of being immune compromised therefore gaining knowledge about how SARS-CoV-2 viruses affecting immune cells in human cancers will provides us new opportunities for preventing or treating virus-associated cancers. Despite COVID-19 pandemic got center stage at present time, however very little research being explores, which increase our knowledge in context with how SARS-CoV-2 infection affect cancer a cellular level. Therefore, in light of the ACE-2 as an important contributor of COVID-19 global, we analyzed correlation between ACE2 and tumor immune infiltration (TIL) level and the type markers of immune cells were investigated in breast cancer subtypes by using TIMER database. Our findings shed light on the immunomodulatory role of ACE2 in the luminal A subtype which may play crucial role in imparting therapeutic resistance in this cancer subtype. 相似文献