全文获取类型
收费全文 | 2692篇 |
免费 | 173篇 |
国内免费 | 1篇 |
专业分类
2866篇 |
出版年
2023年 | 13篇 |
2022年 | 35篇 |
2021年 | 83篇 |
2020年 | 45篇 |
2019年 | 59篇 |
2018年 | 60篇 |
2017年 | 47篇 |
2016年 | 88篇 |
2015年 | 107篇 |
2014年 | 162篇 |
2013年 | 198篇 |
2012年 | 209篇 |
2011年 | 206篇 |
2010年 | 184篇 |
2009年 | 121篇 |
2008年 | 115篇 |
2007年 | 134篇 |
2006年 | 119篇 |
2005年 | 119篇 |
2004年 | 74篇 |
2003年 | 85篇 |
2002年 | 86篇 |
2001年 | 37篇 |
2000年 | 47篇 |
1999年 | 33篇 |
1998年 | 23篇 |
1997年 | 15篇 |
1996年 | 10篇 |
1995年 | 18篇 |
1993年 | 11篇 |
1992年 | 24篇 |
1991年 | 10篇 |
1990年 | 12篇 |
1989年 | 16篇 |
1988年 | 17篇 |
1986年 | 20篇 |
1985年 | 22篇 |
1984年 | 11篇 |
1983年 | 8篇 |
1982年 | 12篇 |
1981年 | 10篇 |
1980年 | 12篇 |
1979年 | 13篇 |
1978年 | 17篇 |
1976年 | 9篇 |
1975年 | 8篇 |
1973年 | 13篇 |
1972年 | 9篇 |
1971年 | 10篇 |
1969年 | 8篇 |
排序方式: 共有2866条查询结果,搜索用时 0 毫秒
41.
Yadlapalli RK Chourasia OP Vemuri K Sritharan M Perali RS 《Bioorganic & medicinal chemistry letters》2012,22(8):2708-2711
A series of dihydropyrimidine derivatives were synthesized by utilizing Biginelli reaction and evaluated for their in vitro anticancer activity against MCF-7 human breast cancer (HBC) cell line using sulforhodamine B (SRB) assay and antitubercular activity against Mycobacterium tuberculosis (MTB) H(37)Rv using Microplate Alamar Blue Assay (MABA). Compounds 13p, 13t were exhibited 70.6% and 63.7% of HBC cell growth inhibition at 10 μM concentration. Interestingly compound 13p was also found to be the most potent in the series against MTB H(37)Rv with MIC value of 0.125 μg/mL. 相似文献
42.
A Copeland A Zeytun M Yassawong M Nolan S Lucas N Hammon S Deshpande JF Cheng C Han R Tapia LA Goodwin S Pitluck K Mavromatis K Liolios I Pagani N Ivanova N Mikhailova A Pati A Chen K Palaniappan M Land L Hauser CD Jeffries EM Brambilla M Rohde J Sikorski R Pukall M Göker JC Detter T Woyke J Bristow JA Eisen V Markowitz P Hugenholtz NC Kyrpides HP Klenk A Lapidus 《Standards in genomic sciences》2012,6(2):240-250
Deinococcus proteolyticus (ex Kobatake et al. 1973) Brook and Murray 1981 is one of currently 47 species in the genus Deinococcus within the family Deinococcaceae. Strain MRP(T) was isolated from feces of Lama glama and possesses extreme radiation resistance, a trait is shares with various other species of the genus Deinococcus, with D. proteolyticus being resistant up to 1.5 Mrad of gamma radiation. Strain MRP(T) is of further interest for its carotenoid pigment. The genome presented here is only the fifth completed genome sequence of a member of the genus Deinococcus (and the forth type strain) to be published, and will hopefully contribute to a better understanding of how members of this genus adapted to high gamma- or UV ionizing-radiation. Here we describe the features of this organism, together with the complete genome sequence and annotation. The 2,886,836 bp long genome with its four large plasmids of lengths 97 kbp, 132 kbp, 196 kbp and 315 kbp harbors 2,741 protein-coding and 58 RNA genes and is a part of the Genomic Encyclopedia of Bacteria and Archaea project. 相似文献
43.
Supratim Ghosh Sumana Mallick Upasana Das Ajay Verma Uttam Pal Sabyasachi Chatterjee Abhishek Nandy Krishna D. Saha Nakul Chandra Maiti Bikash Baishya G. Suresh Kumar William H. Gmeiner 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(3):485-494
We report, based on biophysical studies and molecular mechanical calculations that curcumin binds DNA hairpin in the minor groove adjacent to the loop region forming a stable complex. UV–Vis and fluorescence spectroscopy indicated interaction of curcumin with DNA hairpin. In this novel binding motif, two ? H of curcumin heptadiene chain are closely positioned to the A16-H8 and A17-H8, while G12-H8 is located in the close proximity of curcumin α H. Molecular dynamics (MD) simulations suggest, the complex is stabilized by noncovalent forces including; π-π stacking, H-bonding and hydrophobic interactions. Nuclear magnetic resonance (NMR) spectroscopy in combination with molecular dynamics simulations indicated curcumin is bound in the minor groove, while circular dichroism (CD) spectra suggested minute enhancement in base stacking and a little change in DNA helicity, without significant conformational change of DNA hairpin structure. The DNA:curcumin complex formed with FdU nucleotides rather than Thymidine, demonstrated enhanced cytotoxicity towards oral cancer cells relative to the only FdU substituted hairpin. Fluorescence co-localization demonstrated stability of the complex in biologically relevant conditions, including its cellular uptake. Acridine orange/EtBr staining further confirmed the enhanced cytotoxic effects of the complex, suggesting apoptosis as mode of cell death. Thus, curcumin can be noncovalently complexed to small DNA hairpin for cellular delivery and the complex showed increased cytotoxicity in combination with FdU nucleotides, demonstrating its potential for advanced cancer therapy. 相似文献
44.
The effect of cell density (1–4.5 g L-1) and light intensity (44 and 82 mol m-2 s-1) on fatty acid composition andeicosapentaenoic acid (EPA, 20:5 3) production was studied ina semi-continuous culture of Monodus subterraneus grown in a helicaltubular photobioreactor (`Biocoil') under laboratory conditions. Under lowlight, the highest proportion of EPA (31.5% of total fatty acids) and EPAcontent (3.5% of dry weight), biomass productivity (1.3 g L-124 h-1) and EPA productivity (44 mg L-1 24 h-1)occurred at optimal cell density of about 1.7 g L-1. Cell densityhad no effect on the total fatty acid (TFA) content and was maintained atca. 11% of dry weight. Under high light, the highest proportion ofEPA to fatty acids (31.8%), the total fatty acids content (13.4%) andEPA content (4.3% of dry weight) occurred at cell density of about 3.4gL-1. But the highest biomass productivity (1.7 g L-124 h-1) and EPA productivity (56 mg L-1 24 h-1) wereobtained at a cell density of 1.6 and 2.6g L-1, respectively. Ourresults suggest that manipulating the cell density and light intensity canmodify the composition of fatty acid and production of eicosapentaenoicacid (EPA) in M. subterraneus. 相似文献
45.
Ping Su Vishnu Priya Veeraraghavan Surapaneni Krishna Mohan Wang Lu 《Journal of biochemical and molecular toxicology》2019,33(12)
Zingerone (ZO), an active phenolic agent derived from Zingiber officinale (Ginger), has many pharmacological properties such as antioxidant, antiangiogenic, and antitumor. However, its potential value in cancer and the mechanism by which ZO wields its therapeutic effects remain obscure. Therefore, in this current study, we explored the effects of ZO on suppressing cell proliferation and enhancing apoptosis in colon cancer cells (HCT116). Our results indicated that ZO significantly enhances the production of reactive oxygen species, lipid peroxidation (thiobarbituric acid reactive substance [TBARS]), and loss of cell viability; and reduces mitochondrial membrane potential and antioxidant levels (SOD, CAT, and GSH) in ZO‐treated HCT116 cells in a dose‐dependent (2.5, 5, and 10 µM) manner. Furthermore, ZO induces oxidative stress‐mediated apoptosis as evidenced by apoptotic morphological changes predicted by AO/EtBr, Hoechst staining and further confirmed by comet assay. Moreover, immunoblotting techniques showed that ZO treatment effectively enhances Bax, caspase‐9, and caspase‐3 expressions and decreases the expression of Bcl‐2 in colon cancer cells. Together, our results evidenced that the antitumor effects of ZO reduce cell proliferation and stimulate apoptosis through modulating pro‐ and antiapoptotic molecular events in HCT116 colon cancer cells. Therefore, based on our findings, ZO may be used as a therapeutic agent for the treatment of colon cancer. 相似文献
46.
M ohan , K. 1985. Mycobacterium senegalense from bovines in Eastern Nigeria. Journal of Applied Bacteriology 59 , 277–281.
Detailed characteristics of three mycobacterial strains sharing important properties of Mycobacterium senegalense are described. Their physiological properties were compared with those of a typical M. senegalense strain described by Chamoiseau (1979), six strains of M. senegalense and one typical strain of M. fortuitum from the culture collection of Institute of Microbiology, Rutgers. The three Nigerian strains exhibited minor variations in their physiological properties when compared with other strains of M. senegalense . Unlike the strain of Chamoiseau the Nigerian strains did not utilize benzoate or citrate. The strains were also different from the other six strains of M. senegalense by utilizing trehalose and in failing to produce acid in mannitol. Unlike earlier isolates of M. senegalense the Nigerian strains were not from cases of bovine farcy but from cases with pathological manifestations of pulmonary tuberculosis. They appeared to be intermediate strains between M. senegalense and M. fortuitum . These results raise doubts on the justification for giving specific rank to M. senegalense . 相似文献
Detailed characteristics of three mycobacterial strains sharing important properties of Mycobacterium senegalense are described. Their physiological properties were compared with those of a typical M. senegalense strain described by Chamoiseau (1979), six strains of M. senegalense and one typical strain of M. fortuitum from the culture collection of Institute of Microbiology, Rutgers. The three Nigerian strains exhibited minor variations in their physiological properties when compared with other strains of M. senegalense . Unlike the strain of Chamoiseau the Nigerian strains did not utilize benzoate or citrate. The strains were also different from the other six strains of M. senegalense by utilizing trehalose and in failing to produce acid in mannitol. Unlike earlier isolates of M. senegalense the Nigerian strains were not from cases of bovine farcy but from cases with pathological manifestations of pulmonary tuberculosis. They appeared to be intermediate strains between M. senegalense and M. fortuitum . These results raise doubts on the justification for giving specific rank to M. senegalense . 相似文献
47.
Vashni Gramany Algasan Govender Krishna Bisetty Suren Singh Kugenthiren Permaul 《Journal of biomolecular structure & dynamics》2016,34(8):1681-1692
The aim of this study was to clone, express, and characterize a β-xylosidase (Tlxyn1) from the thermophilic fungus Thermomyces lanuginosus SSBP in Pichia pastoris GS115 as well as analyze optimal activity and stability using computational and experimental methods. The enzyme was constitutively expressed using the GAP promoter and secreted into the medium due to the alpha-mating factor secretion signal present on the expression vector pBGPI. The 1276 bp gene consists of an open reading frame that does not contain introns. A 12% SDS–PAGE gel revealed a major protein band at an estimated molecular mass of 50 kDa which corresponded to zymogram analysis. The three-dimensional structure of β-xylosidase was predicted, and molecular dynamics simulations at different ranges of temperature and pH were performed in order to predict optimal activity and folding energy. The results suggested a strong conformational temperature and pH dependence. The recombinant enzyme exhibited optimal activity at pH 7 and 50°C and retained 80% activity at 50°C, pH 7 for about 45 min. This is the first report of the cloning, functional expression, and simulations study of a β-xylosidase from Thermomyces species in a fungal host. 相似文献
48.
49.
S. Hari Krishna K. C. Sekhar Rao J. Suresh Babu D. Srirami Reddy S. Hari Krishna 《Bioprocess and biosystems engineering》2000,22(5):467-470
High yielding mutant strain, Trichoderma reesei QM-9414, was employed for the cellulase enzyme production. Enzyme production conditions (pH, inoculum age and concentration, and organic supplements) were optimized. The ability of partially purified enzyme to hydrolyze various regionally abundant lignocellulosic raw materials was studied. Enzymatic hydrolysis conditions (temperature, pH, enzyme and substrate concentrations) were optimized. Temperature 50v°C, pH 4.5, enzyme concentration 40 FPU/g substrate and substrate concentration 2.5% were found to be optimum for the maximum yields of sugars. #-glucosidase supplementation was found to increase both the sugar yield and hydrolysis rate, and shorten the reaction time significantly. 相似文献
50.
Krishna M. Boini Min Xia Justin M. Abais Guangbi Li Ashley L. Pitzer Todd W.B. Gehr Yang Zhang Pin-Lan Li 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2014
Inflammasome, an intracellular inflammatory machinery, has been reported to be involved in a variety of chronic degenerative diseases such as atherosclerosis, autoinflammatory diseases and Alzheimer's disease. The present study hypothesized that the formation and activation of inflammasomes associated with apoptosis associated speck-like protein (ASC) are an important initiating mechanism resulting in obesity-associated podocyte injury and consequent glomerular sclerosis. To test this hypothesis, Asc gene knockout (Asc−/−), wild type (Asc+/+) and intrarenal Asc shRNA-transfected wild type (Asc shRNA) mice were fed a high fat diet (HFD) or normal diet (ND) for 12 weeks to produce obesity and associated glomerular injury. Western blot and RT-PCR analyses demonstrated that renal tissue Asc expression was lacking in Asc−/− mice or substantially reduced in Asc shRNA transfected mice compared to Asc+/+ mice. Confocal microscopic and co-immunoprecipitation analysis showed that the HFD enhanced the formation of inflammasome associated with Asc in podocytes as shown by colocalization of Asc with Nod-like receptor protein 3 (Nalp3). This inflammasome complex aggregation was not observed in Asc−/− and local Asc shRNA-transfected mice. The caspase-1 activity, IL-1β production and glomerular damage index (GDI) were also significantly attenuated in Asc−/− and Asc shRNA-transfected mice fed the HFD. This decreased GDI in Asc−/− and Asc shRNA transfected mice on the HFD was accompanied by attenuated proteinuria, albuminuria, foot process effacement of podocytes and loss of podocyte slit diaphragm molecules. In conclusion, activation and formation of inflammasomes in podocytes are importantly implicated in the development of obesity-associated glomerular injury. 相似文献