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171.
172.
173.
W. Grant Waugh 《BMJ (Clinical research ed.)》1941,2(4206):236-238
174.
Early intermediates in the denaturation of hemoglobin, termed hemichromes, have been found previously to associate with the cytoplasmic domain of erythrocyte membrane band 3 in a manner which rapidly propagates into an insoluble, macroscopic copolymer. Because this interaction is thought to force a redistribution of band 3 in situ, the properties of the copolymerization reaction were investigated in greater detail. The band 3-hemichrome coaggregate was found to be stabilized largely by ionic interactions since elevation of either ionic strength or pH led to dissolution of the complex. The pH dependence, however, shifted to a more alkaline pH with increasing hemichrome concentration, suggesting a strong linkage between band 3 or hemichrome protonation and copolymer formation. The stoichiometry of the copolymer was measured at five globin chains per band 3 chain whenever underivatized dimer-tetramer hemichrome mixtures were employed. However, cross-linking of the hemichromes at either the alpha or the beta chains to form the stabilized tetramer yielded a copolymer stoichiometry of approximately eight globin chains per band 3 chain, i.e., two hemichrome sites per band 3 subunit. While underivatized hemichromes exhibited both a fast and slow phase of copolymerization, the cross-link-stabilized tetrameric hemichromes displayed predominantly the fast phase kinetics. Naturally occurring disulfide cross-linked hemichromes also reacted more avidly with band 3 than their reduced counterparts; however, the copolymerization process also proceeded to completion with totally reduced components. It is concluded that copolymerization of band 3 with hemichromes should occur under normal cellular conditions and at an accelerated velocity when the intracellular reducing power is low. 相似文献
175.
Douglas Waugh 《CMAJ》1967,96(13):947-953
The experience of evaluation of both students and course in pathology at Dalhousie Medical School indicates that valuable reproducible and probably objective information is obtained by the use of frequent multiple-choice tests combined with substantial final oral examinations. Course evaluation by student questionnaires has provided useful information on course modifications and teaching techniques. The most informative feature of the evaluation program is in the provision of mechanisms for feedback from students to faculty and among faculty members. By these means weaknesses in teaching have been identified and often corrected. The method has aided in the early identification of poor students and of their areas of weakness so that remedial instruction can be instituted before the final examination. 相似文献
176.
177.
Kong YX Van Bergen N Trounce IA Bui BV Chrysostomou V Waugh H Vingrys A Crowston JG 《Aging cell》2011,10(4):572-583
Mouse models that accumulate high levels of mitochondrial DNA (mtDNA) mutations owing to impairments in mitochondrial polymerase γ (PolG) proofreading function have been shown to develop phenotypes consistent with accelerated aging. As increase in mtDNA mutations and aging are risk factors for neurodegenerative diseases, we sought to determine whether increase in mtDNA mutations renders neurons more vulnerable to injury. We therefore examined the in vivo functional activity of retinal neurons and their ability to cope with stress in transgenic mice harboring a neural‐targeted mutant PolG gene with an impaired proofreading capability (Kasahara, et al. (2006) Mol Psychiatry 11 (6):577–93, 523). We confirmed that the retina of these transgenic mice have increased mtDNA deletions and point mutations and decreased expression of mitochondrial oxidative phosphorylation enzymes. Associated with these changes, the PolG transgenic mice demonstrated accelerated age‐related loss in retinal function as measured by dark‐adapted electroretinogram, particularly in the inner and middle retina. Furthermore, the retinal ganglion cell–dominant inner retinal function in PolG transgenic mice showed greater vulnerability to injury induced by raised intraocular pressure, an insult known to produce mechanical, metabolic, and oxidative stress in the retina. These findings indicate that an accumulation of mtDNA mutations is associated with impairment in neural function and reduced capacity of neurons to resist external stress in vivo, suggesting a potential mechanism whereby aging central nervous system can become more vulnerable to neurodegeneration. 相似文献
178.
Waugh JL Celver J Sharma M Dufresne RL Terzi D Risch SC Fairbrother WG Neve RL Kane JP Malloy MJ Pullinger CR Gu HF Tsatsanis C Hamilton SP Gold SJ Zachariou V Kovoor A 《PloS one》2011,6(11):e27984
Regulator of G protein signaling 9-2 (RGS9-2) is a protein that is highly enriched in the striatum, a brain region that mediates motivation, movement and reward responses. We identified a naturally occurring 5 nucleotide deletion polymorphism in the human RGS9 gene and found that the mean body mass index (BMI) of individuals with the deletion was significantly higher than those without. A splicing reporter minigene assay demonstrated that the deletion had the potential to significantly decrease the levels of correctly spliced RGS9 gene product. We measured the weights of rats after virally transduced overexpression of RGS9-2 or the structurally related RGS proteins, RGS7, or RGS11, in the nucleus accumbens (NAc) and observed a reduction in body weight after overexpression of RGS9-2 but not RGS7 or 11. Conversely, we found that the RGS9 knockout mice were heavier than their wild-type littermates and had significantly higher percentages of abdominal fat. The constituent adipocytes were found to have a mean cross-sectional area that was more than double that of corresponding cells from wild-type mice. However, food intake and locomotion were not significantly different between the two strains. These studies with humans, rats and mice implicate RGS9-2 as a factor in regulating body weight. 相似文献
179.
Our understanding of the interaction of leukocytes and the vessel wall during leukocyte capture is limited by an incomplete understanding of the mechanical properties of the endothelial surface layer. It is known that adhesion molecules on leukocytes are distributed non-uniformly relative to surface topography 3, that topography limits adhesive bond formation with other surfaces 9, and that physiological contact forces (≈ 5.0 − 10.0 pN per microvillus) can compress the microvilli to as little as a third of their resting length, increasing the accessibility of molecules to the opposing surface 3, 7. We consider the endothelium as a two-layered structure, the relatively rigid cell body, plus the glycocalyx, a soft protective sugar coating on the luminal surface 6. It has been shown that the glycocalyx can act as a barrier to reduce adhesion of leukocytes to the endothelial surface 4. In this report we begin to address the deformability of endothelial surfaces to understand how the endothelial mechanical stiffness might affect bond formation. Endothelial cells grown in static culture do not express a robust glycocalyx, but cells grown under physiological flow conditions begin to approximate the glycocalyx observed in vivo
2. The modulus of the endothelial cell body has been measured using atomic force microscopy (AFM) to be approximately 5 to 20 kPa 5. The thickness and structure of the glycocalyx have been studied using electron microscopy 8, and the modulus of the glycocalyx has been approximated using indirect methods, but to our knowledge, there have been no published reports of a direct measurement of the glycocalyx modulus in living cells. In this study, we present indentation experiments made with a novel AFM probe on cells that have been cultured in conditions to maximize their glycocalyx expression to make direct measurements of the modulus and thickness of the endothelial glycocalyx. 相似文献
180.
Linda Sharp Seonaidh Cotton Julian Little Nicola M. Gray Margaret Cruickshank Louise Smart Alison Thornton Norman Waugh Leslie Walker 《PloS one》2013,8(12)