全文获取类型
收费全文 | 187篇 |
免费 | 10篇 |
出版年
2022年 | 2篇 |
2021年 | 3篇 |
2019年 | 1篇 |
2018年 | 4篇 |
2017年 | 4篇 |
2016年 | 4篇 |
2015年 | 8篇 |
2014年 | 11篇 |
2013年 | 16篇 |
2012年 | 23篇 |
2011年 | 15篇 |
2010年 | 13篇 |
2009年 | 3篇 |
2008年 | 8篇 |
2007年 | 5篇 |
2006年 | 5篇 |
2005年 | 7篇 |
2004年 | 9篇 |
2003年 | 7篇 |
2002年 | 9篇 |
2001年 | 5篇 |
2000年 | 1篇 |
1999年 | 2篇 |
1998年 | 5篇 |
1997年 | 4篇 |
1996年 | 1篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1991年 | 5篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1984年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1969年 | 1篇 |
排序方式: 共有197条查询结果,搜索用时 199 毫秒
61.
Lack of Adjustment Latitude at Work as a Trigger of Taking Sick Leave—A Swedish Case-Crossover Study
Hanna Hultin Johan Hallqvist Kristina Alexanderson Gun Johansson Christina Lindholm Ingvar Lundberg Jette M?ller 《PloS one》2013,8(4)
Objectives
Research has shown that individuals reporting a low level of adjustment latitude, defined as having few possibilities to temporarily adjust work demands to illness, have a higher risk of sick leave. To what extent lack of adjustment latitude influences the individual when making the decision to take sick leave is unknown. We hypothesize that ill individuals are more likely to take sick leave on days when they experience a lack of adjustment latitude at work than on days with access to adjustment latitude.Methods
A case-crossover design was applied to 546 sick-leave spells, extracted from a cohort of 1 430 employees at six Swedish workplaces, with a 3–12 month follow-up of all new sick-leave spells. Exposure to lack of adjustment latitude on the first sick-leave day was compared with exposure during several types of control periods sampled from the previous two months for the same individual.Results
Only 35% of the respondents reported variations in access to adjustment latitude, and 19% reported a constant lack of adjustment latitude during the two weeks prior to the sick-leave spell. Among those that did report variation, the risk of sick leave was lower on days with lack of adjustment latitude, than on days with access (Odds Ratio 0.36, 95% Confidence Interval 0.25–0.52).Conclusions
This is the first study to show the influence of adjustment latitude on the decision to take sick leave. Among those with variations in exposure, lack of adjustment latitude was a deterrent of sick leave, which is contrary to the à priori hypothesis. These results indicate that adjustment latitude may not only capture long-lasting effects of a flexible working environment, but also temporary possibilities to adjust work to being absent. Further studies are needed to disentangle the causal mechanisms of adjustment latitude on sick-leave. 相似文献62.
Kulahin N Kristensen O Rasmussen KK Olsen L Rydberg P Vestergaard B Kastrup JS Berezin V Bock E Walmod PS Gajhede M 《Structure (London, England : 1993)》2011,19(2):203-211
The ectodomain of olfactory cell adhesion molecule (OCAM/NCAM2/RNCAM) consists of five immunoglobulin (Ig) domains (IgI-V), followed by two fibronectin-type 3 (Fn3) domains (Fn3I-II). A complete structural model of the entire ectodomain of human OCAM has been assembled from crystal structures of six recombinant proteins corresponding to different regions of the ectodomain. The model is the longest experimentally based composite structural model of an entire IgCAM ectodomain. It displays an essentially linear arrangement of IgI-V, followed by bends between IgV and Fn3I and between Fn3I and Fn3II. Proteins containing IgI-IgII domains formed stable homodimers in solution and in crystals. Dimerization could be disrupted in?vitro by mutations in the dimer interface region. In conjunction with the bent ectodomain conformation, which can position IgI-V parallel with the cell surface, the IgI-IgII dimerization enables OCAM-mediated trans-interactions with an intercellular distance of about 20?nm, which is consistent with that observed in synapses. 相似文献
63.
64.
Amino acid and glucose metabolism in fed‐batch CHO cell culture affects antibody production and glycosylation 下载免费PDF全文
65.
A multi‐pronged investigation into the effect of glucose starvation and culture duration on fed‐batch CHO cell culture 下载免费PDF全文
66.
Jette G. Petersen Rikke Bergmann Povl Krogsgaard-Larsen Thomas Balle Bente Frølund 《Neurochemical research》2014,39(6):1005-1015
The ionotropic GABAA receptors (GABAARs) are widely distributed in the central nervous system where they play essential roles in numerous physiological and pathological processes. A high degree of structural heterogeneity of the GABAAR has been revealed and extensive effort has been made to develop selective and potent GABAAR agonists. This review investigates the use of heterocyclic carboxylic acid bioisosteres within the GABAAR area. Several heterocycles including 3-hydroxyisoxazole, 3-hydroxyisoxazoline, 3-hydroxyisothiazole, and the 1- and 3-hydroxypyrazole rings have been employed in order to map the orthosteric binding site. The physicochemical properties of the heterocyclic moieties making them suitable for bioisosteric replacement of the carboxylic acid in the molecule of GABA are discussed. A variety of synthetic strategies for synthesis of the heterocyclic scaffolds are available. Likewise, methods for introduction of substituents into specific positions of the heterocyclic scaffolds facilitate the investigation of different regions in the orthosteric binding pocket in close vicinity of the core scaffolds of muscimol/GABA. The development of structural models, from pharmacophore models to receptor homology models, has provided more insight into the molecular basis for binding. Similar binding modes are proposed for the heterocyclic GABA analogues covered in this review by use of ligand–receptor docking into the receptor homology model and the presented structure–activity relationships. A network of interactions between the analogues and the binding pocket is leaving no room for substituents and underline the limited space in the GABAAR orthosteric binding site when in the agonist conformation. 相似文献
67.
Anas Al-Khawaja Jette G. Petersen Maria Damgaard Mette H. Jensen Stine B. Vogensen Maria E. K. Lie Bolette Kragholm Hans Bräuner-Osborne Rasmus P. Clausen Bente Frølund Petrine Wellendorph 《Neurochemical research》2014,39(10):1988-1996
The γ-aminobutyric acid (GABA) transporters (GATs) are key membrane transporter proteins involved in the termination of GABAergic signaling at synapses in the mammalian brain and proposed drug targets in neurological disorders such as epilepsy. To date, four different GAT subtypes have been identified: GAT1, GAT2, GAT3 and the betaine/GABA transporter 1 (BGT1). Owing to the lack of potent and subtype selective inhibitors of the non-GAT1 GABA transporters, the physiological role and therapeutic potential of these transporters remain to be fully understood. Based on bioisosteric replacement of the amino group in β-alanine or GABA, a series of compounds was generated, and their pharmacological activity assessed at human GAT subtypes. Using a cell-based [3H]GABA uptake assay, several selective inhibitors at human BGT1 were identified. The guanidine-containing compound 9 (2-amino-1,4,5,6-tetrahydropyrimidine-5-carboxylic acid hydrochloride) displayed more than 250 times greater potency than the parent compound β-alanine at BGT1 and is thus the most potent inhibitor reported to date for this subtype (IC50 value of 2.5 µM). In addition, compound 9 displayed about 400, 16 and 40 times lower inhibitory potency at GAT1, GAT2 and GAT3, respectively. Compound 9 was shown to be a substrate for BGT1 and to have an overall similar pharmacological profile at the mouse orthologue. Compound 9 constitutes an interesting pharmacological tool for specifically investigating the cellular pharmacology of BGT1 and is the first small-molecule substrate identified with such a high selectivity for BGT1 over the three other GAT subtypes. 相似文献
68.
69.
Background
Studies have shown that long-term sick leave is a strong predictor of disability pension. However, few have aimed to disentangle the effect of sick leave and of health status.The objective of this study was to investigate whether there is an association between long-term sick leave and disability pension and unemployment, when taking health status into account.Methods/Principal Findings
The study was based on the Stockholm Public Health Cohort, restricted to 13,027 employed individuals (45.9% men) aged 18–59 in 2002 and followed until 2007.Hazard ratios (HR) with 95% Confidence Interval (CI) were estimated by Cox regression models adjusting for socio-demographic factors and five measures of health status.Having been on long-term sick leave increased the risk of disability pension (HR 4.01; 95% CI 3.19–5.05) and long-term unemployment (HR 1.45; 95% CI 1.05–2.00), after adjustment for health status. The analyses of long-term sick leave due to specific illness showed that the increased risk for long-term unemployment was confined to the group on sick leave due to musculoskeletal (HR 1.70 95% CI 1.00–2.89) and mental illness (HR 1.80 95% CI 1.13–2.88) and further that there was an increased risk for short-term unemployment in the group on sick leave due to mental illness (HR1.57 95%CI 1.09–2.26).Conclusions/Significance
Long-term sick leave increases the risks of both disability pension and unemployment even when taking health status into account. The results support the hypothesis that long-term sick leave may start a process of marginalization from the labor market. 相似文献70.
Luo Q Wypych J Jiang XG Zhang X Luo S Jerums M Lewis J Iii RK Huang G Apostol I 《Analytical biochemistry》2012,421(2):517-525
In this report, we examine the performance of a mass spectrometry (MS)-based method for quantification of protein posttranslational modifications (PTMs) using stable isotope labeled internal standards. Uniform labeling of proteins and highly similar behavior of the labeled vs nonlabeled analyte pairs during chromatographic separation and electrospray ionization (ESI) provide the means to directly quantify a wide range of PTMs. In the companion report (Jiang et al., Anal. Biochem., 421 (2012) 506-516.), we provided principles and example applications of the method. Here we show satisfactory accuracy and precision for quantifying protein modifications by using the SILIS method when the analyses were performed on different types of mass spectrometers, such as ion-trap, time-of-flight (TOF), and quadrupole instruments. Additionally, the stable isotope labeled internal standard (SILIS) method demonstrated an extended linear range of quantification expressed in accurate quantification up to at least a 4 log concentration range on three different types of mass spectrometers. We also demonstrate that lengthy chromatographic separation is no longer required to obtain quality results, offering an opportunity to significantly shorten the method run time. The results indicate the potential of this methodology for rapid and large-scale assessment of multiple quality attributes of a therapeutic protein in a single analysis. 相似文献