全文获取类型
收费全文 | 143篇 |
免费 | 21篇 |
专业分类
164篇 |
出版年
2021年 | 6篇 |
2020年 | 3篇 |
2019年 | 2篇 |
2018年 | 2篇 |
2017年 | 2篇 |
2016年 | 2篇 |
2015年 | 9篇 |
2014年 | 4篇 |
2013年 | 7篇 |
2012年 | 8篇 |
2011年 | 8篇 |
2010年 | 6篇 |
2009年 | 8篇 |
2008年 | 6篇 |
2007年 | 6篇 |
2006年 | 10篇 |
2005年 | 5篇 |
2004年 | 6篇 |
2003年 | 5篇 |
2002年 | 8篇 |
2001年 | 6篇 |
2000年 | 4篇 |
1999年 | 2篇 |
1998年 | 2篇 |
1997年 | 2篇 |
1996年 | 8篇 |
1994年 | 1篇 |
1993年 | 3篇 |
1992年 | 5篇 |
1991年 | 4篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1986年 | 1篇 |
1976年 | 1篇 |
1937年 | 1篇 |
1932年 | 1篇 |
1929年 | 3篇 |
1928年 | 1篇 |
1926年 | 1篇 |
1909年 | 1篇 |
排序方式: 共有164条查询结果,搜索用时 0 毫秒
1.
5''-Nucleotidases in rat heart. Evidence for the occurrence of two soluble enzymes with different substrate specificities. 总被引:7,自引:3,他引:4 下载免费PDF全文
Chromatography of soluble proteins from rat heart on phosphocellulose columns separates two 5'-nucleotidases. The first to emerge from the column shows a preference for AMP over IMP as substrate, whereas the second shows a preference for IMP over AMP. The properties of the IMP-preferring enzyme, including the conditions under which it is eluted from phosphocellulose columns, show it to be the enzyme studied by Itoh, Oka & Ozasa [Biochem. J. (1986) 235, 847-851]. The kinetic properties of the AMP-preferring enzyme indicate that it is likely to be the enzyme responsible for the production of adenosine under conditions of hypoxia and increased work load, and with metabolic stresses such as a high load of acetate. 相似文献
2.
The physiological function of von Willebrand's factor depends on its tubular storage in endothelial Weibel-Palade bodies 总被引:4,自引:0,他引:4
Michaux G Abbitt KB Collinson LM Haberichter SL Norman KE Cutler DF 《Developmental cell》2006,10(2):223-232
Weibel-Palade bodies are the 1-5 microm long rod-shaped storage organelles of endothelial cells. We have investigated the determinants and functional significance of this shape. We find that the folding of the hemostatic protein von Willebrand's factor (VWF) into tubules underpins the rod-like shape of Weibel-Palade bodies. Further, while the propeptide and the N-terminal domains of mature VWF are sufficient to form tubules, their maintenance relies on a pH-dependent interaction between the two. We show that the tubular conformation of VWF is essential for a rapid unfurling of 100 microm long, platelet-catching VWF filaments when exposed to neutral pH after exocytosis in cell culture and in living blood vessels. If tubules are disassembled prior to exocytosis, then short or tangled filaments are released and platelet recruitment is reduced. Thus, a 100-fold compaction of VWF into tubules determines the unique shape of Weibel-Palade bodies and is critical to this protein's hemostatic function. 相似文献
3.
Objectives
How medical students handle negative emotions expressed by simulated patients during Objective Structured Clinical Examinations (OSCE) has not been fully investigated. We aim to explore (i) whether medical students respond differently to different types of patients’ emotional cues; and (2) possible effects of patients’ progressive disclosure of emotional cues on students’ responses.Methods
Forty OSCE consultations were video recorded and coded for patients’ expressions of emotional distress and students’ responses using a validated behavioural coding scheme (the Verona Coding Definitions of Emotional Sequence). Logistic multilevel regression was adopted to model the probability of the occurrence of student reduce space response behaviour as a function of the number of patients’ expressions of emotional cues.Results
We found that medical students offered responses that differed to emotional cue types expressed by simulated patients. Students appeared to provide space to emotional cues when expressed in vague and unspecific words and reduce space to cues emphasizing physiological or cognitive correlates. We also found that medical students were less likely to explore patients’ emotional distress nearer the end of the consultation and when the duration of a patient speech turn got larger. Cumulative frequency of patients’ emotional cues also predicted students’ reduce space behaviour.Practical Implications
Understanding how medical students manage negative emotions has significant implications for training programme development focusing on emotion recognition skills and patient-centred communication approach. In addition, the statistical approaches adopted by this study will encourage researchers in healthcare communication to search for appropriate analytical techniques to test theoretical propositions. 相似文献4.
Samuel J. Clark Kathleen Kahn Brian Houle Adriane Arteche Mark A. Collinson Stephen M. Tollman Alan Stein 《PLoS medicine》2013,10(3)
Background
There is evidence that a young child''s risk of dying increases following the mother''s death, but little is known about the risk when the mother becomes very ill prior to her death. We hypothesized that children would be more likely to die during the period several months before their mother''s death, as well as for several months after her death. Therefore we investigated the relationship between young children''s likelihood of dying and the timing of their mother''s death and, in particular, the existence of a critical period of increased risk.Methods and Findings
Data from a health and socio-demographic surveillance system in rural South Africa were collected on children 0–5 y of age from 1 January 1994 to 31 December 2008. Discrete time survival analysis was used to estimate children''s probability of dying before and after their mother''s death, accounting for moderators. 1,244 children (3% of sample) died from 1994 to 2008. The probability of child death began to rise 6–11 mo prior to the mother''s death and increased markedly during the 2 mo immediately before the month of her death (odds ratio [OR] 7.1 [95% CI 3.9–12.7]), in the month of her death (OR 12.6 [6.2–25.3]), and during the 2 mo following her death (OR 7.0 [3.2–15.6]). This increase in the probability of dying was more pronounced for children whose mothers died of AIDS or tuberculosis compared to other causes of death, but the pattern remained for causes unrelated to AIDS/tuberculosis. Infants aged 0–6 mo at the time of their mother''s death were nine times more likely to die than children aged 2–5 y. The limitations of the study included the lack of knowledge about precisely when a very ill mother will die, a lack of information about child nutrition and care, and the diagnosis of AIDS deaths by verbal autopsy rather than serostatus.Conclusions
Young children in lower income settings are more likely to die not only after their mother''s death but also in the months before, when she is seriously ill. Interventions are urgently needed to support families both when the mother becomes very ill and after her death. Please see later in the article for the Editors'' Summary 相似文献5.
6.
7.
8.
Deville K Gold VA Robson A Whitehouse S Sessions RB Baldwin SA Radford SE Collinson I 《The Journal of biological chemistry》2011,286(6):4659-4669
Protein secretion in bacteria is driven through the ubiquitous SecYEG complex by the ATPase SecA. The structure of SecYEG alone or as a complex with SecA in detergent reveal a monomeric heterotrimer enclosing a central protein channel, yet in membranes it is dimeric. We have addressed the functional significance of the oligomeric status of SecYEG in protein translocation using single molecule and ensemble methods. The results show that while monomers are sufficient for the SecA- and ATP-dependent association of SecYEG with pre-protein, active transport requires SecYEG dimers arranged in the back-to-back conformation. Molecular modeling of this dimeric structure, in conjunction with the new functional data, provides a rationale for the presence of both active and passive copies of SecYEG in the functional translocon. 相似文献
9.
Miller KA Barrow J Collinson JM Davidson S Lear M Hill RE Mackenzie A 《Developmental biology》2007,311(2):665-678
The product of the Msx1 gene is a potent inhibitor of muscle differentiation. Msx1 is expressed in muscle precursor cells of the limb bud that also express Pax3. It is thought that Msx1 may facilitate distal migration by delaying myogenesis in these cells. Despite the role played by Msx1 in inhibiting muscle differentiation, nothing is known of the mechanisms that support the expression of the Msx1 gene within limb bud muscle precursor cells. In the present study we have used a combination of comparative genomics, mouse transgenic analysis, in situ hybridisation and immunohistochemistry to identify a highly conserved and tissue-specific regulatory sub-domain within the previously characterised Msx1 gene proximal enhancer element that supports the expression of the Msx1 gene in Pax3-expressing mouse limb pre-muscle masses. Furthermore, using a combination of in situ hybridisation, in vivo ChIP assay and transgenic explant culture analysis we provide evidence that Msx1 expression in limb bud muscle precursor cells is dependent on the canonical Wnt/TCF signalling pathway that is important in muscle shape formation. The results of these studies provide evidence of a mechanistic link between the Wnt/TCF and the Msx1/Pax3/MyoD pathways within limb bud muscle precursor cells. 相似文献
10.
Recombinant murine MRP14 (mMRP14) was produced in Escherichia coli using the pGEX expression system. The mass of fusion protein, by electrospray ionization-mass spectrometry (ESI/MS), was 39,213 Da which compares well with the theoretical mass (39,210.4 Da). Thrombin digestion of fusion protein was expected at a cloned thrombin consensus sequence (. LVPRGS. ) located between glutathione S-transferase and mMRP14. Analysis of products of digestion by C4 reverse-phase HPLC and SDS-PAGE/Western blotting revealed two immunoreactive cleavage products with molecular weights around 13, 000. Masses of the two proteins determined by ESI/MS were 13,062 and 11,919 Da. The larger product corresponded to the expected mass of recombinant mMRP14 (13,061.9 Da). Analysis of the protein sequence of recombinant mMRP14 revealed a thrombin-like consensus sequence (. NNPRGH. ) located close to the C-terminus. The smaller protein corresponded to a truncated form of rec mMRP14 (rec MRP141-102) with a calculated mass of 11,918.6 Da. Optimization of the cleavage conditions resulted in >95% full-length rec mMRP14. Native mMRP14 contains one intramolecular disulfide bond between Cys79 and Cys90. The full-length recombinant protein was renatured and oxidized in ammonium acetate (pH approximately 7) for 96 h and formed >95% of the native intramolecular disulfide-bonded form. MRP141-102 bound substantially less 65Zn2+ compared to native mMRP14 or rec mMRP14 after transfer to polyvinylidene difluoride and incubation with 65ZnCl2, implicating the His residues located within the C-terminal domain in Zn2+ binding. 相似文献