全文获取类型
收费全文 | 440篇 |
免费 | 23篇 |
出版年
2022年 | 4篇 |
2021年 | 6篇 |
2020年 | 3篇 |
2019年 | 2篇 |
2018年 | 7篇 |
2017年 | 6篇 |
2016年 | 11篇 |
2015年 | 14篇 |
2014年 | 18篇 |
2013年 | 25篇 |
2012年 | 31篇 |
2011年 | 35篇 |
2010年 | 17篇 |
2009年 | 14篇 |
2008年 | 21篇 |
2007年 | 22篇 |
2006年 | 16篇 |
2005年 | 12篇 |
2004年 | 10篇 |
2003年 | 20篇 |
2002年 | 13篇 |
2001年 | 16篇 |
2000年 | 17篇 |
1999年 | 16篇 |
1998年 | 5篇 |
1997年 | 4篇 |
1996年 | 5篇 |
1995年 | 9篇 |
1994年 | 8篇 |
1993年 | 5篇 |
1992年 | 5篇 |
1991年 | 5篇 |
1990年 | 4篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1985年 | 7篇 |
1984年 | 4篇 |
1982年 | 2篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1978年 | 2篇 |
1977年 | 3篇 |
1975年 | 3篇 |
1974年 | 3篇 |
1973年 | 1篇 |
1972年 | 4篇 |
1970年 | 6篇 |
1969年 | 2篇 |
1965年 | 2篇 |
排序方式: 共有463条查询结果,搜索用时 15 毫秒
371.
Ma X Tan ST Khoo CL Sim HM Chan LW Chui WK 《Bioorganic & medicinal chemistry letters》2011,21(18):5428-5431
The emergence and spread of multidrug-resistant strains of Staphylococcus aureus and Mycobacterium tuberculosis are generating a threat to public health worldwide. In the current study, a series of N(1)-benzyl and N(1)-benzyloxy-1,6-dihydro-1,3,5-triazine-2,4-diamine derivatives were synthesized and investigated for their antimicrobial activity against S. aureus, and Mycobacterium smegmatis which is taxonomically related to M. tuberculosis. Most of the compounds exhibited good activity against M. smegmatis as determined by comparison of diameters of the zone of inhibition of test compounds and standard antibiotics. Compound 7o showed potent antimycobacterial activity against M. smegmatis without mammalian DHFR inhibition liability. The results from this study indicate that 1-benzyl derivatives of 1,6-dihydro-1,3,5-triazine-2,4-diamines may be used as lead compounds for the discovery of antimycobacterial agents. 相似文献
372.
Relative quantification of in vitro gene expression using real-time PCR requires stably expressed reference gene for normalisation.
In this study, total RNA from MCF7, HCT116 and HepG2 cells were extracted and converted to cDNA using commercially available
kit, and real-time PCR was then performed to analyse the expression levels of twelve reference genes to select the most ideal
reference gene for accurate normalisation in gene expression study. geNorm and NormFinder software were used to analyse the
stabilities of the reference genes, which showed a wide range of Ct values. The geNorm analysis showed the following ranking for stability of genes: UBC, YWHAZ > RPLP > TBP > ACTB > HPRT1 > PPIA > GAPDH > GUSB > B2M > TUBB > RRN18S.
A similar ranking of reference genes was obtained by NormFinder, and the four most stable reference genes were identical using
both approaches. UBC and YWHAZ were proposed to be the two most suitable reference genes based on the above analyses. To further
assess the stabilities of the UBC and YWHAZ in a formal experiment, MCF7, HCT116 and HepG2 cell lines were subjected to treatments
with 5-aza-dC and TSA. Both UBC and YWHAZ exhibited stable expression levels across control and treatment groups. Therefore,
we propose that UBC and YWHAZ are the two most suitable reference genes for our gene expression studies using MCF7, HCT116
and HepG2 cell lines. 相似文献
373.
Al Ghouleh I Khoo NK Knaus UG Griendling KK Touyz RM Thannickal VJ Barchowsky A Nauseef WM Kelley EE Bauer PM Darley-Usmar V Shiva S Cifuentes-Pagano E Freeman BA Gladwin MT Pagano PJ 《Free radical biology & medicine》2011,51(7):1271-1288
Reactive oxygen species (ROS) are involved in numerous physiological and pathophysiological responses. Increasing evidence implicates ROS as signaling molecules involved in the propagation of cellular pathways. The NADPH oxidase (Nox) family of enzymes is a major source of ROS in the cell and has been related to the progression of many diseases and even environmental toxicity. The complexity of this family's effects on cellular processes stems from the fact that there are seven members, each with unique tissue distribution, cellular localization, and expression. Nox proteins also differ in activation mechanisms and the major ROS detected as their product. To add to this complexity, mounting evidence suggests that other cellular oxidases or their products may be involved in Nox regulation. The overall redox and metabolic status of the cell, specifically the mitochondria, also has implications on ROS signaling. Signaling of such molecules as electrophilic fatty acids has an impact on many redox-sensitive pathologies and thus, as anti-inflammatory molecules, contributes to the complexity of ROS regulation. This review is based on the proceedings of a recent international Oxidase Signaling Symposium at the University of Pittsburgh's Vascular Medicine Institute and Department of Pharmacology and Chemical Biology and encompasses further interaction and discussion among the presenters. 相似文献
374.
The usual practice of using a control chart to monitor a process is to take samples from the process with fixed sampling interval (FSI). In this paper, a synthetic control chart with the variable sampling interval (VSI) feature is proposed for monitoring changes in the process mean. The VSI synthetic chart integrates the VSI chart and the VSI conforming run length (CRL) chart. The proposed VSI synthetic chart is evaluated using the average time to signal (ATS) criterion. The optimal charting parameters of the proposed chart are obtained by minimizing the out-of-control ATS for a desired shift. Comparisons between the VSI synthetic chart and the existing , synthetic , VSI and EWMA charts, in terms of ATS, are made. The ATS results show that the VSI synthetic chart outperforms the other type charts for detecting moderate and large shifts. An illustrative example is also presented to explain the application of the VSI synthetic chart. 相似文献
375.
Yong Cheng-Chung Khoo Boon-Yin Sasidharan Sreenivasan Piyawattanametha Wibool Kim Sae-Hun Khemthongcharoen Numfon Chuah Li-Oon Ang May-Yen Liong Min-Tze 《Annals of microbiology》2015,65(2):1037-1047
This study aimed to evaluate anti-staphylococcal properties of crude and fractionated extracts of lactic acid bacteria (LAB) isolated from local meat, dairy, and fermented products. A total of 36 LAB isolates were obtained and identified via 16S rDNA sequencing. Cell-free supernatant (CFS) of all isolates exhibiting a statistically significant inhibition against Staphylococcus aureus (ρ < 0.05), with six LAB isolates exhibiting a more prevalent inhibition. The inhibition effects of cell wall and intracellular extracts from the six prevalent isolates were evaluated. Lactobacillus plantarum USM8613 was the most prominent isolate with both CFS and cell wall extract exhibiting the most prevalent inhibition against S. aureus. Scanning electron micrographs showed alteration of S. aureus membrane morphology upon CFS treatment, suggesting an anti-staphylococcal effect via membrane destruction. Confocal laser scanning micrographs showed inhibition against biofilm formations by S. aureus in porcine skins upon CFS treatment. The CFS from L. plantarum USM8613 was separated into protein, lipid, and polysaccharide fractions for evaluation of anti-staphylococcal activity and chemical characterization. All fractions inhibited growth of S. aureus (ρ < 0.05), with protein fractions exhibiting stronger inhibition effect. Data from our present study showed that extracts from LAB could be applied as biopreservatives in the food industries and/or as an antimicrobial agent against bacterial infections for cosmeceutical and pharmaceutical uses. 相似文献
376.
Leow Soon-Sen Lee Wei-Kang Khoo Jia-Shiun Teoh Seddon Hoh Chee-Choong Fairus Syed Sambanthamurthi Ravigadevi Hayes K. C. 《Molecular biology reports》2020,47(12):9409-9427
Molecular Biology Reports - The Nile rat (Arvicanthis niloticus) is a novel diurnal carbohydrate-sensitive rodent useful for studies on type 2 diabetes mellitus (T2DM) and the metabolic syndrome.... 相似文献
377.
378.
Khoo AL Chai LY Koenen HJ Oosting M Steinmeyer A Zuegel U Joosten I Netea MG van der Ven AJ 《Cytokine》2011,55(2):294-300
A well-known association between vitamin D(3) and infection with Mycobacterium tuberculosis has previously been reported, but little is known regarding the underlying mechanisms. We have investigated how 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] affects the proinflammatory cytokine production induced by M. tuberculosis. Furthermore, we explored whether 1,25(OH)(2)D(3) influence the production of the protective antimycobacterial peptide cathelicidin. Upon in vitro stimulation with M. tuberculosis, 1,25(OH)(2)D(3) induced a dose-dependent down-regulation of IL-6, TNFα and IFNγ, while increasing the production of IL-10 in culture supernatant as well as cathelicidin mRNA expression. This effect on cytokine response was not due to modulation of T-helper cell differentiation, as T-bet, GATA3, Foxp3 and ROR-γt mRNA expression remained unaffected. Similarly, 1,25(OH)(2)D(3) did not affect suppressor of cytokine signaling (SOCS)1 and SOCS3 mRNA expression. The mechanism whereby 1,25(OH)(2)D(3) inhibited the proinflammatory cytokine response was through reduced expression of the pattern recognition receptors (PRR) - TLR2, TLR4, Dectin-1 and mannose receptor, whose mRNA and protein expression were both reduced. The suppression of PRRs could be restored by a VDR antagonist. Upon M. tuberculosis stimulation, 1,25(OH)(2)D(3) modulates the balance in cytokine production towards an anti-inflammatory profile by repression of TLR2, TLR4, Dectin-1 and mannose receptor expression, while increasing cathelicidin production. These two effects may have beneficial consequences, by reducing the collateral tissue damage induced by proinflammatory cytokines, while the antibacterial effects of cathelicidin are enhanced. 相似文献
379.
Chin LF Kong SM Seng HL Khoo KS Vikneswaran R Teoh SG Ahmad M Khoo SB Maah MJ Ng CH 《Journal of inorganic biochemistry》2011,105(3):339-347
The synthesis and characterization of two cobalt(II) complexes, Co(phen)(ma)Cl 1 and Co(ma)2(phen) 2, (phen = 1,10-phenanthroline, ma− = maltolate or 2-methyl-4-oxo-4H-pyran-3-olate) are reported herein. The complexes have been characterized by FTIR, CHN analysis, fluorescence spectroscopy, UV-visible spectroscopy, conductivity measurement and X-ray crystallography. The number of chelated maltolate ligands seems to influence their DNA recognition, topoisomerase I inhibition and antiproliferative properties. 相似文献
380.
The bioactive components of Ganoderma formosanum have not yet been characterized. We investigated the immunomodulatory activities of the extracellular polysaccharides produced
from a submerged mycelial culture of G. formosanum. The polysaccharides were mainly composed of d-mannose, d-galactose and d-glucose. After gel filtration chromatography, three polysaccharide fractions (PS-F1, PS-F2 and PS-F3) were purified. PS-F2
stimulated mouse RAW264.7 macrophages to produce TNF-α and nitric oxide, and enhanced the phagocytic activity of macrophages.
PS-F2 challenge in mice triggered an acute inflammatory response characterized by the recruitment of neutrophils and monocytes,
which protected mice from subsequent infection of Listeria monocytogenes. The results indicate that the heteropolysaccharides produced by G. formosanum can activate the innate immune response on macrophages. 相似文献