全文获取类型
收费全文 | 267篇 |
免费 | 26篇 |
出版年
2022年 | 5篇 |
2021年 | 13篇 |
2020年 | 6篇 |
2019年 | 9篇 |
2018年 | 7篇 |
2017年 | 7篇 |
2016年 | 13篇 |
2015年 | 17篇 |
2014年 | 13篇 |
2013年 | 12篇 |
2012年 | 19篇 |
2011年 | 15篇 |
2010年 | 15篇 |
2009年 | 10篇 |
2008年 | 13篇 |
2007年 | 14篇 |
2006年 | 15篇 |
2005年 | 14篇 |
2004年 | 4篇 |
2003年 | 9篇 |
2002年 | 10篇 |
2001年 | 3篇 |
2000年 | 3篇 |
1999年 | 2篇 |
1998年 | 12篇 |
1997年 | 3篇 |
1996年 | 1篇 |
1995年 | 4篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1989年 | 6篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1983年 | 1篇 |
1980年 | 2篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1975年 | 1篇 |
1973年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有293条查询结果,搜索用时 31 毫秒
21.
Ching Yu Austin Huang Joel Studebaker Anton Yuryev Jianping Huang Kathryn E Scott Jennifer Kuebler Shobha Varde Steven Alfisi Craig A Gelfand Mark Pohl Michael T Boyce-Jacino 《BMC bioinformatics》2004,5(1):1-10
Background
SNP genotyping typically incorporates a review step to ensure that the genotype calls for a particular SNP are correct. For high-throughput genotyping, such as that provided by the GenomeLab SNPstream® instrument from Beckman Coulter, Inc., the manual review used for low-volume genotyping becomes a major bottleneck. The work reported here describes the application of a neural network to automate the review of results.Results
We describe an approach to reviewing the quality of primer extension 2-color fluorescent reactions by clustering optical signals obtained from multiple samples and a single reaction set-up. The method evaluates the quality of the signal clusters from the genotyping results. We developed 64 scores to measure the geometry and position of the signal clusters. The expected signal distribution was represented by a distribution of a 64-component parametric vector obtained by training the two-layer neural network onto a set of 10,968 manually reviewed 2D plots containing the signal clusters.Conclusion
The neural network approach described in this paper may be used with results from the GenomeLab SNPstream instrument for high-throughput SNP genotyping. The overall correlation with manual revision was 0.844. The approach can be applied to a quality review of results from other high-throughput fluorescent-based biochemical assays in a high-throughput mode. 相似文献22.
The purpose of this research was to improve the solubility and therefore dissolution and bioavailability of triamterene, a
poorly water soluble diuretic, by complexation with β-cyclodextrin. Triamterene has been reported to show low bioavailability
after oral administration, with wide intersubject variation. This study presents the formulation of solid dispersions of triamterene
with β-cyclodextrin—by cogrinding, kneading, and coevaporation, using low pH conditions—and their characterizations, evaluation
of improvement in dissolution profiles, and in vivo advantage. Phase solubility studies indicated complex with possible stoichiometry
of 1∶1 and a stability constant of 167.67M−1. The solid dispersions were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance, x-ray diffraction,
and differential scanning calorimetry studies. The characterization studies confirmed inclusion of the phenyl ring of triamterene
within the nonpolar cavity of β-cyclodextrin in the coevaporate. Remarkable improvement in in vitro drug release profiles
in 0.1 N HCl and pH 6.8 phosphate buffer was observed with all dispersions, especially the coevaporate. The coevaporate, when
administered orally in rats, also exhibited improved in vivo activity, as measured by net sodium ion excretion, as compared
with triamterene powder. Thus, coevaporation of the drug and β-cyclodextrin from acidified alcohol provide the optimum condition
for inclusion complexation to give a binary system with remarkable improvement in in vitro drug release profile and in vivo
performance. 相似文献
23.
24.
Cadherin adhesion molecules function in numerous cell biological processes that influence embryo development, normal cell physiology, and pathophysiology of many disease processes. Cadherins nucleate the assembly of the adherens junction, a cell-to-cell adhesion plaque that is prominent in simple epithelial cells and found in many cell types. Numerous cell biological approaches have been used to study this interesting class of molecules. Here, we outline methodology used in our studies of junctional complexes to examine effects of signaling molecules on assembly mechanisms. This is a quantitative method that allows the investigator to test the combined effect of two different signaling processes to determine whether these two signals act in concert within the same pathway. We discuss how this method could be generalized to other studies to examine consequences of various experimental manipulations on the assembly of cellular structures. 相似文献
25.
Dengue fever is the most prevalent arboviral disease in the tropical and sub-tropical regions of the world. The present report describes molecular detection and serotyping of dengue viruses in acute phase blood samples collected from New Delhi, India. Phylogenetic and molecular clock analysis of dengue virus serotype 1 and 3 strains were also investigated. Dengue virus infection was detected in 68.87% out of 604 samples tested by RT-PCR between 2011 & 2014. Dengue serotype 1 was detected in 25.48% samples, dengue serotype 2 in 79.56% samples and dengue serotype 3 in 11.29% samples. Dengue serotype 4 was not detected. Co-infection by more than one dengue serotype was detected in 18.26% samples. Envelope gene of 29 DENV-1 and 14 DENV-3 strains were sequenced in the study. All the DENV-1 strains grouped with the American African genotype. All DENV-3 strains were found to belong to Genotype III. Nucleotide substitution rates of dengue 1 and 3 viruses were determined in the study. Time to the most recent common ancestor (TMRCA) of dengue 1 viruses was determined to be 132 years. TMRCA of DENV-3 viruses was estimated to be 149 years. Bayesian skyline plots were constructed for Indian DENV-1 and 3 strains which showed a decrease in population size since 2005 in case of DENV- 1 strains while no change was observed in recent years in case of DENV-3 strains. The study also revealed a change in the dominating serotype in Delhi, India in recent years. The study will be helpful in formulating control strategies for the outbreaks. In addition, it will also assist in tracking the movement and evolution of this emerging virus. 相似文献
26.
27.
28.
High-temperature biotrickling filtration of hydrogen sulphide 总被引:1,自引:0,他引:1
Biofiltration of malodorous reduced sulphur compounds such as hydrogen sulphide has been confined to emissions that are at
temperatures below 40°C despite the fact that there are many industrial emissions (e.g. in the pulp and paper industry) at
temperatures well above 40°C. This paper describes our study on the successful treatment of hydrogen sulphide gas at temperatures
of 40, 50, 60 and 70°C using a microbial community obtained from a hot spring. Three biotrickling filter (BTF) systems were
set up in parallel for a continuous run of 9 months to operate at three different temperatures, one of which was always at
40°C as a mesophilic control and the other two were for exploring high-temperature operation up to 70°C. The continuous experiment
and a series of batch experiments in glass bottles (250 ml) showed that addition of glucose and monosodium glutamate enhanced
thermophilic biofiltration of hydrogen sulphide gas and a removal rate of 40 g m−3 h−1 was achieved at 70°C. We suggest that the glucose is acting as a carbon source for the existing microbial community in the
BTFs, whereas glutamate is acting as a compatible solute. The use of such organic compounds to enhance biodegradation of hydrogen
sulphide, particularly at high temperatures, has not been demonstrated to our knowledge and, hence, has opened up a range
of possibilities for applying biofiltration to hot gas effluent. 相似文献
29.
Oo ML Thangada S Wu MT Liu CH Macdonald TL Lynch KR Lin CY Hla T 《The Journal of biological chemistry》2007,282(12):9082-9089
Sphingosine 1-phosphate (S1P), a multifunctional lipid mediator, regulates lymphocyte trafficking, vascular permeability, and angiogenesis by activation of the S1P1 receptor. This receptor is activated by FTY720-P, a phosphorylated derivative of the immunosuppressant and vasoactive compound FTY720. However, in contrast to the natural ligand S1P, FTY720-P appears to act as a functional antagonist, even though the mechanisms involved are poorly understood. In this study, we investigated the fate of endogenously expressed S1P1 receptor in agonist-activated human umbilical vein endothelial cells and human embryonic kidney 293 cells expressing green fluorescent protein-tagged S1P1. We show that FTY720-P is more potent than S1P at inducing receptor degradation. Pretreatment with an antagonist of S1P1, VPC 44116, prevented receptor internalization and degradation. FTY720-P did not induce degradation of internalization-deficient S1P1 receptor mutants. Further, small interfering RNA-mediated down-regulation of G protein-coupled receptor kinase-2 and beta-arrestins abolished FTY720-P-induced S1P1 receptor degradation. These data suggest that agonist-induced phosphorylation of S1P1 and subsequent endocytosis are required for FTY720-P-induced degradation of the receptor. S1P1 degradation is blocked by MG132, a proteasomal inhibitor. Indeed, FTY720-P strongly induced polyubiquitinylation of S1P1 receptor, whereas S1P at concentrations that induced complete internalization was not as efficient, suggesting that receptor internalization is required but not sufficient for ubiquitinylation and degradation. We propose that the ability of FTY720-P to target the S1P1 receptor to the ubiquitinylation and proteasomal degradation pathway may at least in part underlie its immunosuppressive and anti-angiogenic properties. 相似文献
30.
EC Costa A Moreira B Cavalcanti K Krinski MS Aoki 《Biology of sport / Institute of Sport》2015,32(1):35-40
The present study investigated the effect of unilateral and bilateral resistance exercise (RE) on maximal voluntary strength, total volume of load lifted (TVLL), rating of perceived exertion (RPE) and blood lactate concentration of resistance-trained males. Twelve healthy men were assessed for the leg extension one-repetition maximum (1RM) strength using bilateral and unilateral contractions. Following this assessment, an RE session (3 sets of repetitions to failure) was conducted with bilateral and unilateral (both limbs) contractions using a load of 50% 1RM. The TVLL was calculated by the product of the number of repetitions and the load lifted per repetition. RPE and blood lactate were measured before, during and after each set. Session RPE was measured 30 minutes after RE sessions. There was a significant difference in the bilateral (120.0±11.9) and unilateral (135.0±20.2 kg) 1RM strength (p < 0.05). The TVLL was similar between both RE sessions. Although the repetitions decreased with each successive set, the total number of repetitions completed in the bilateral protocol (48) was superior to the unilateral (40) protocol (p < 0.05). In both bouts, RPE increased with each subsequent set whilst blood lactate increased after set 1 and thereafter remained stable (p < 0.05). The RPE and lactate responses were not significantly different between both sessions. In conclusion, a bilateral deficit in leg extension strength was confirmed, but the TVLL was similar between both RE sessions when exercising to voluntary fatigue. This outcome could be attributed to the number of repetitions completed in the unilateral RE bout. The equal TVLL would also explain the similar perceptual and metabolic responses across each RE session. 相似文献