全文获取类型
收费全文 | 477篇 |
免费 | 31篇 |
国内免费 | 2篇 |
出版年
2023年 | 13篇 |
2022年 | 10篇 |
2021年 | 30篇 |
2020年 | 20篇 |
2019年 | 27篇 |
2018年 | 24篇 |
2017年 | 21篇 |
2016年 | 18篇 |
2015年 | 42篇 |
2014年 | 40篇 |
2013年 | 37篇 |
2012年 | 22篇 |
2011年 | 25篇 |
2010年 | 14篇 |
2009年 | 13篇 |
2008年 | 12篇 |
2007年 | 16篇 |
2006年 | 13篇 |
2005年 | 12篇 |
2004年 | 9篇 |
2003年 | 17篇 |
2002年 | 7篇 |
2001年 | 2篇 |
1999年 | 2篇 |
1996年 | 2篇 |
1994年 | 2篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1988年 | 2篇 |
1986年 | 2篇 |
1984年 | 4篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1981年 | 4篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1977年 | 4篇 |
1976年 | 2篇 |
1975年 | 4篇 |
1973年 | 5篇 |
1972年 | 3篇 |
1970年 | 1篇 |
1969年 | 3篇 |
1968年 | 2篇 |
1967年 | 2篇 |
1966年 | 1篇 |
1964年 | 1篇 |
1960年 | 1篇 |
1937年 | 1篇 |
排序方式: 共有510条查询结果,搜索用时 32 毫秒
51.
Berthouze M Ayoub M Russo O Rivail L Sicsic S Fischmeister R Berque-Bestel I Jockers R Lezoualc'h F 《FEBS letters》2005,579(14):2973-2980
Serotonin 5-HT4 receptor isoforms are G protein-coupled receptors (GPCRs) with distinct pharmacological properties and may represent a valuable target for the treatment of many human disorders. Here, we have explored the process of dimerization of human 5-HT4 receptor (h5-HT4R) by means of co-immunoprecipitation and bioluminescence resonance energy transfer (BRET). Constitutive h5-HT4(d)R dimer was observed in living cells and membrane preparation of CHO and HEK293 cells. 5-HT4R ligands did not influence the constitutive energy transfer of the h5-HT4(d)R splice variant in intact cells and isolated plasma membranes. In addition, we found that h5-HT4(d)R and h5-HT4(g)R which structurally differ in the length of their C-terminal tails were able to form constitutive heterodimers independently of their activation state. Finally, we found that coexpression of h5-HT4R and beta2-adrenergic receptor (beta2AR) led to their heterodimerization. Given the large number of h5-HT4R isoforms which are coexpressed in a same tissue, our results points out the complexity by which this 5-HTR sub-type mediates its biological effects. 相似文献
52.
53.
Neghal Kandiyil Nishath Altaf Akram A. Hosseini Shane T. MacSweeney Dorothee P. Auer 《PloS one》2012,7(10)
Background and Purpose
Women are at lower risk of stroke, and appear to benefit less from carotid endarterectomy (CEA) than men. We hypothesised that this is due to more benign carotid disease in women mediating a lower risk of recurrent cerebrovascular events. To test this, we investigated sex differences in the prevalence of MRI detectable plaque hemorrhage (MRI PH) as an index of plaque instability, and secondly whether MRI PH mediates sex differences in the rate of cerebrovascular recurrence.Methods
Prevalence of PH between sexes was analysed in a single centre pooled cohort of 176 patients with recently symptomatic, significant carotid stenosis (106 severe [≥70%], 70 moderate [50–69%]) who underwent prospective carotid MRI scanning for identification of MRI PH. Further, a meta-analysis of published evidence was undertaken. Recurrent events were noted during clinical follow up for survival analysis.Results
Women with symptomatic carotid stenosis (50%≥) were less likely to have plaque hemorrhage (PH) than men (46% vs. 70%) with an adjusted OR of 0.23 [95% CI 0.10–0.50, P<0.0001] controlling for other known vascular risk factors. This negative association was only significant for the severe stenosis subgroup (adjusted OR 0.18, 95% CI 0.067–0.50) not the moderate degree stenosis. Female sex in this subgroup also predicted a longer time to recurrent cerebral ischemic events (HR 0.38 95% CI 0.15–0.98, P = 0.045). Further addition of MRI PH or smoking abolished the sex effects with only MRI PH exerting a direct effect.Meta-analysis confirmed a protective effect of female sex on development of PH: unadjusted OR for presence of PH = 0.54 (95% CI 0.45–0.67, p<0.00001).Conclusions
MRI PH is significantly less prevalent in women. Women with MRI PH and severe stenosis have a similar risk as men for recurrent cerebrovascular events. MRI PH thus allows overcoming the sex bias in selection for CEA. 相似文献54.
55.
Sexuality in fungi has long been a matter of concerns and debates that always necessitated extensive analysis of the relationship between organisms assumed to represent different developmental forms of the same organism. Moreover, mating-virulence correlation and the growing worry of opportunistic fungal infections in immunocompromised states associated with AIDS, cancer chemotherapy and organ transplantation protocols have been critically addressed nowadays. In view of that, we genetically characterized Aspergillus chevalieri, Aspergillus nidulans, Aspergillus tetrazonus (quadrilineatus) and their teleomorphs with RAPD analysis using 5'-d[AACGCGCAAC]-3' and 5'-d[CCCGTCAGCA]-3' primers. The reported similarities between the sexual and the asexual forms of the tested species, using Dice coefficient, ranged between 40% and 70% which holds pretty much with the current systematics of the genus. The study presents a rapid consistent method for identification of A. chevalieri, A. nidulans, A. tetrazonus (quadrilineatus) and their teleomorphs based on the banding pattern of RAPD-generated fragments that can be reliably used ahead of further applications on these species. 相似文献
56.
Marker genotype data and grain and malt quality phenotype data from three barley (Hordeum vulgare L.) mapping populations were used to investigate the feasibility of selective genotyping for detection of quantitative trait loci (QTLs). With selective genotyping, only individuals with high and low phenotypic values for the trait of interest are genotyped. Here, genotyping of 10 to 70% of each population (i.e., 5 to 35% in each tail of the phenotypic distribution) was considered. Genomic positions detected by selective genotyping were compared to QTL position estimates from interval mapping analysis using marker genotype data from the entire population. Selective genotyping reliably detected almost all of the mapped QTLs, often with only 10% of the population genotyped. Selective genotyping also detected spurious QTLs in regions of the genome where no significant QTL had been mapped. Even with additional genotyping to verify putative QTLs, the total genotyping effort for detection of QTLs for a single trait by selective genotyping was usually less than 30% of that required for conventional interval mapping. Simultaneous investigation of two or more traits by selective genotyping would require additional genotyping effort, but could still be worthwhile. 相似文献
57.
Bassam M. Ayoub Yasmeen M. Attia 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):858-866
Chemical entities with structural diversity were introduced as candidates targeting adenosine receptor with different clinical activities, containing 3,7-dihydro-1H-purine-2,6-dione, especially adenosine 3 receptors (ADORA3). Our initial approach started with pharmacophore screening of ADORA3 modulators; to choose linagliptin (LIN), approved anti-diabetic drug as Dipeptidyl peptidase-4 inhibitors, to be studied for its modulating effect towards ADORA3. This was followed by generation, purification, analytical method development, and structural elucidation of oxidative degraded product (DEG). Both of LIN and DEG showed inhibitory profile against hepatocellular carcinoma cell lines with induction of apoptosis at G2/M phase with increase in caspase-3 levels, accompanied by a downregulation in gene and protein expression levels of ADORA3 with a subsequent increase in cAMP. Quantitative in vitro assessment of LIN binding affinity against ADORA3 was also performed to exhibit inhibitory profile at Ki of 37.7?nM. In silico molecular modelling showing binding affinity of LIN and DEG towards ADORA3 was conducted. 相似文献
58.
59.
Akram Najafi Mojtaba Hasanpour Azam Askary Masoud Aziemzadeh Najmeh Hashemi 《Folia microbiologica》2018,63(3):335-343
The present study was aimed at investigating the relationship between the new Clermont’s phylogenetic groups, virulence factors, and pathogenicity island markers (PAIs) among uropathogenic Escherichia coli (UPEC) in Iran. This cross-sectional study was carried out on 140 UPEC isolates collected from patients with urinary tract infections in Bushehr, Iran. All isolates were subjected to phylogenetic typing using a new quadruplex-PCR method. The presence of PAI markers and virulence factors in UPEC strains was evaluated by multiplex PCR. The most predominant virulence gene was fimH (85%), followed by iucC (61.4%), papC (38.6%), hlyA (22.1%), cnf-1 (18.6%), afa (10.7%), papG and neuC (each 9.3%), ibeA (3.6%), and sfa/foc (0.7%). The most common phylogenetic group was related to B2 (39.3%), and the least common to A (0.7%). The most prevalent PAI marker was PAI IV536 (77.14%), while markers for PAI III536 (13.57%), PAI IIJ96 (12.86%), and PAI II536 (12.14%) were the least frequent among the UPEC strains. Meanwhile, the PAI IJ96 marker was not detected. There was a significant association between the phylogenetic group B2 and all the studied virulence genes and PAI markers. To our knowledge, this is the first study to compare the relationship between new phylogenetic groups, virulence genes and PAI markers in UPEC strains in Iran. The phylogenetic group B2 was predominantly represented among the studied virulence genes and PAI markers, indicating the preference of particular strains to carry virulence genes. 相似文献
60.
Factorial design optimization of micelle enhanced synchronous spectrofluorimetric assay of Omarigliptin: Applied to content uniformity testing and in vitro drug release
下载免费PDF全文
![点击此处可从《Luminescence》网站下载免费的PDF全文](/ch/ext_images/free.gif)
A micelle enhanced spectrofluorimetric method was developed for determination of Omarigliptin (OMG) based on its native fluorescence behavior. The interaction of OMG with surfactants and macromolecules was studied. In aqueous solution, the relative fluorescence intensity (RFI) of OMG was enhanced by 24% in the presence of Tween 80 at pH 3.5. The optimal conditions for the micelle enhanced fluorescence were attained by Minitab® program using Plackett–Burman factorial design. Pareto chart, contour plots and surface plots were used to exclude the insignificant variables and optimize the significant factors. The spectrofluorimeter was operated under synchronous mode using ?λ = 30 nm and recording the RFI of the intense narrow band at 267 nm for OMG in 0.5% w/v Tween 80 + 0.2 M acetate buffer (pH 3.5) system using water as diluent. Using synchronous scan mode offered many advantages including considerable reduction of spectral overlap and enhanced linearity of the calibrators. Validation parameters were satisfied over the concentration range 0.1–2 μg/ml. The developed method was the first analytical procedure for OMG assay in Marizev® tablets. Moreover, content uniformity testing and in vitro drug release of tablets were performed. 相似文献