全文获取类型
收费全文 | 246篇 |
免费 | 21篇 |
国内免费 | 1篇 |
专业分类
268篇 |
出版年
2022年 | 3篇 |
2021年 | 5篇 |
2020年 | 2篇 |
2018年 | 4篇 |
2017年 | 2篇 |
2016年 | 2篇 |
2015年 | 6篇 |
2014年 | 12篇 |
2013年 | 12篇 |
2012年 | 11篇 |
2011年 | 10篇 |
2010年 | 13篇 |
2009年 | 11篇 |
2008年 | 6篇 |
2007年 | 11篇 |
2006年 | 9篇 |
2005年 | 10篇 |
2004年 | 15篇 |
2003年 | 11篇 |
2002年 | 7篇 |
2001年 | 5篇 |
2000年 | 4篇 |
1999年 | 8篇 |
1998年 | 6篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 4篇 |
1988年 | 4篇 |
1987年 | 3篇 |
1985年 | 3篇 |
1983年 | 3篇 |
1982年 | 4篇 |
1978年 | 3篇 |
1977年 | 3篇 |
1976年 | 2篇 |
1973年 | 7篇 |
1972年 | 6篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1969年 | 3篇 |
1968年 | 4篇 |
1967年 | 2篇 |
1966年 | 1篇 |
1965年 | 4篇 |
1945年 | 1篇 |
排序方式: 共有268条查询结果,搜索用时 0 毫秒
91.
Xing Liu Jiaqiang Qin Qing Luo Yang Bi Gaohui Zhu Wei Jiang Stephanie H. Kim Mi Li Yuxi Su Guoxin Nan Jing Cui Wenwen Zhang Ruidong Li Xiang Chen Yuhan Kong Jiye Zhang Jinhua Wang Mary Rose Rogers Hongyu Zhang Wei Shui Chen Zhao Ning Wang Xi Liang Ningning Wu Yunfeng He Hue H. Luu Rex C. Haydon Lewis L. Shi Tingyu Li Tong‐Chuan He Ming Li 《Journal of cellular and molecular medicine》2013,17(9):1160-1172
Mesenchymal stem cells (MSCs) are multipotent progenitors, which give rise to several lineages, including bone, cartilage and fat. Epidermal growth factor (EGF) stimulates cell growth, proliferation and differentiation. EGF acts by binding with high affinity to epidermal growth factor receptor (EGFR) on the cell surface and stimulating the intrinsic protein tyrosine kinase activity of its receptor, which initiates a signal transduction cascade causing a variety of biochemical changes within the cell and regulating cell proliferation and differentiation. We have identified BMP9 as one of the most osteogenic BMPs in MSCs. In this study, we investigate if EGF signalling cross‐talks with BMP9 and regulates BMP9‐induced osteogenic differentiation. We find that EGF potentiates BMP9‐induced early and late osteogenic markers of MSCs in vitro, which can be effectively blunted by EGFR inhibitors Gefitinib and Erlotinib or receptor tyrosine kinase inhibitors AG‐1478 and AG‐494 in a dose‐ and time‐dependent manner. Furthermore, EGF significantly augments BMP9‐induced bone formation in the cultured mouse foetal limb explants. In vivo stem cell implantation experiment reveals that exogenous expression of EGF in MSCs can effectively potentiate BMP9‐induced ectopic bone formation, yielding larger and more mature bone masses. Interestingly, we find that, while EGF can induce BMP9 expression in MSCs, EGFR expression is directly up‐regulated by BMP9 through Smad1/5/8 signalling pathway. Thus, the cross‐talk between EGF and BMP9 signalling pathways in MSCs may underline their important roles in regulating osteogenic differentiation. Harnessing the synergy between BMP9 and EGF should be beneficial for enhancing osteogenesis in regenerative medicine. 相似文献
92.
Hudson PJ Dobson AP Cattadori IM Newborn D Haydon DT Shaw DJ Benton TG Grenfell BT 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2002,357(1425):1259-1271
While the concept of population growth rate has been of central importance in the development of the theory of population dynamics, few empirical studies consider the intrinsic growth rate in detail, let alone how it may vary within and between populations of the same species. In an attempt to link theory with data we take two approaches. First, we address the question ''what growth rate patterns does theory predict we should see in time-series?'' The models make a number of predictions, which in general are supported by a comparative study between time-series of harvesting data from 352 red grouse populations. Variations in growth rate between grouse populations were associated with factors that reflected the quality and availability of the main food plant of the grouse. However, while these results support predictions from theory, they provide no clear insight into the mechanisms influencing reductions in population growth rate and regulation. In the second part of the paper, we consider the results of experiments, first at the individual level and then at the population level, to identify the important mechanisms influencing changes in individual productivity and population growth rate. The parasitic nematode Trichostrongylus tenuis is found to have an important influence on productivity, and when incorporated into models with their patterns of distribution between individuals has a destabilizing effect and generates negative growth rates. The hypothesis that negative growth rates at the population level were caused by parasites was demonstrated by a replicated population level experiment. With a sound and tested model framework we then explore the interaction with other natural enemies and show that in general they tend to stabilize variations in growth rate. Interestingly, the models show selective predators that remove heavily infected individuals can release the grouse from parasite-induced regulation and allow equilibrium populations to rise. By contrast, a tick-borne virus that killed chicks simply leads to a reduction in the equilibrium. When humans take grouse they do not appear to stabilize populations and this may be because many of the infective stages are available for infection before harvesting commences. In our opinion, an understanding of growth rates and population dynamics is best achieved through a mechanistic approach that includes a sound experimental approach with the development of models. Models can be tested further to explore how the community of predators and others interact with their prey. 相似文献
93.
M W Carpenter S P Sady M A Sady B Haydon D R Coustan P D Thompson 《Journal of applied physiology》1990,68(3):1173-1176
We examined the effect of maternal weight gain during pregnancy on exercise performance. Ten women performed submaximal cycle (up to 60 W) and treadmill (4 km/h, up to 10% grade) exercise tests at 34 +/- 1.5 (SD) wk gestation and 7.6 +/- 1.7 wk postpartum. Postpartum subjects wearing weighted belts designed to equal their body weight during the antepartum tests performed two additional treadmill tests. Absolute O2 uptake (VO2) at the same work load was higher during pregnancy than postpartum during cycle (1.04 +/- 0.08 vs. 0.95 +/- 0.09 l/min, P = 0.014), treadmill (1.45 +/- 0.19 vs. 1.27 +/- 0.20 l/min, P = 0.0002), and weighted treadmill (1.45 +/ 0.19 vs. 1.36 +/- 0.20 l/min, P = 0.04) exercise. None of these differences remained, however, when VO2 was expressed per kilogram of body weight. Maximal VO2 (VO2max) estimated from the individual heart rate-VO2 curves was the same during and after pregnancy during cycling (1.96 +/- 0.37 to 1.98 +/- 0.39 l/min), whereas estimated VO2max increased postpartum during treadmill (2.04 +/- 0.38 to 2.21 +/- 0.36 l/min, P = 0.03) and weighted treadmill (2.04 +/- 0.38 to 2.19 +/- 0.38 l/min, P = 0.03) exercise. We conclude that increased body weight during pregnancy compared with the postpartum period accounts for 75% of the increased VO2 during submaximal weight-bearing exertion in pregnancy and contributes to reduced exercise capacity. The postpartum increase in estimated VO2max during weight-bearing exercise is the result of consistently higher antepartum heart rates during all submaximal work loads. 相似文献
94.
The purpose of the present study was to characterise the structure dynamics of pure salivary secretions retained on controlled surfaces with different surface energies in the early stage of salivary film formation. Germanium prisms prepared to have either low surface energy or medium surface energy were incubated in fresh secretions of either human parotid saliva (HPS) or human submandibular/sublingual saliva (HSMSLS) for 15, 90, and 180 min. After controlled rinsing with distilled water, the surfaces were air dried and thereafter imaged with atomic force microscopy (AFM). The amount of adsorbed material and the size of the structures detected increased with increased saliva exposure time. The film thicknesses varied from 10 to 150 nm, and both HPS and HSMSLS films contained structures with diameters varying from 40 nm to 2 μm. Some of these were clustered into special formations. The HPS films exhibited a more granular morphology than the HSMSLS films. Furthermore, branched lines were detected on the low surface energy germanium prisms incubated in saliva. The results indicate that exposure time, surface energy, and type of salivary secretion all are factors affecting the adsorption characteristics of salivary films. 相似文献
95.
Daniel Haydon Susan Lea Liz Fry Nick Knowles Alan R. Samuel David Stuart Mark E. J. Woolhouse 《Journal of molecular evolution》1998,46(4):465-475
The VP1 capsid protein of foot and mouth disease virus (FMDV) is highly polymorphic and contains several of the major immunogenic
sites important to effective antibody neutralization and subsequent viral clearance by the immune system. Whether this high
level of polymorphism is of adaptive value to the virus remains unknown. In this study we examined sequence data from a set
of 55 isolates in order to establish the nature of selective pressures acting on this gene. Using the known molecular structure
of VP1, the rates and ratios of different types of nonsynonymous and synonymous changes were compared between different parts
of the protein. All parts of the protein are subject to purifying selection, but this is greatest amongst those amino acid
residues within β-strands and is significantly reduced at residues exposed on the capsid surface, which include those residues
demonstrated by previous mutational analyses to permit the virus to escape from monoclonal antibody binding. The ratios of
nonsynonymous substitution resulting in various forms of physicochemically radical and conserved amino acid change were shown
to be largely equal throughout these different parts of the protein. There was a consistently higher level of nonsynonymous
and charge radical sites in those regions of the gene coding for residues exposed on the outer surface of the capsid and a
marked difference in the use of amino acids between surface and nonsurface regions of the protein. However, the analysis is
consistent with the hypothesis that the observed sequence variation arises where it is least likely to be disruptive to the
higher-order structure of the protein and is not necessarily due to positive Darwinian selection.
Received: 8 March 1997 / Accepted: 12 August 1997 相似文献
96.
Thermodynamic considerations show that the adsorption of nonpolar molecules into lipid bilayer membranes should depend upon the curvature of the membranes. Estimations of the differences in adsorption of a small n-alkane between a planar phospholipid bilayer and liposomal vesicles have been attempted. For spherical multilamellar liposomes exposed to saturated solutions of alkane in water the adsorption is calculated to be 17-65% of the value for the planar bilayer, depending on the assumptions in the model. 相似文献
97.
The specific conductances of black lipid membranes of lecithin, glycerylmonooleate and lecithin and cholesterol in aqueous solutions of KCl + nonactin have been measured. The relative conductances of the lecithin and the glycerylmonooleate membranes are accurately accounted for by the difference in their surface potentials. The large effect of cholesterol in depressing the conductance of the lecithin membranes is, however, not accounted for by changes in the surface potential and it is necessary to invoke either changes in the membrane solubility of the nonactin-K+ complex, or changes in the membrane viscosity (as experiences by the ionophore in transit), or both.The surface potentials which, in all the present membranes, arise solely from layers of oriented molecular dipoles, are not affected by the KCl concentration. 相似文献
98.
Fate of Labeled Hydroxamates During Iron Transport from Hydroxamate-Iron Chelates 总被引:1,自引:1,他引:0 下载免费PDF全文
Jean E. L. Arceneaux W. B. Davis D. N. Downer A. H. Haydon B. R. Byers 《Journal of bacteriology》1973,115(3):919-927
The fate of the hydroxamic acid-iron transport cofactors during iron uptake from the (59)Fe(3+) chelates of the (3)H-labeled hydroxamates schizokinen and aerobactin was studied by assay of simultaneous incorporation of both (59)Fe(3+) and (3)H. In the schizokinen-producing organism Bacillus megaterium ATCC 19213 transport of (59)Fe(3+) from the (3)H-schizokinen-(59)Fe(3+) chelate at 37 C was accompanied by rapid uptake and release (within 2 min) of (3)H-schizokinen, although (3)H-schizokinen discharge was temperature-dependent and did not occur at 0 C. In the schizokinen-requiring strain B. megaterium SK11 similar release of (3)H-schizokinen occurred only at elevated concentrations of the double-labeled chelate; at lower chelate concentrations, (3)H-schizokinen remained cell-associated. Temperature-dependent uptake of deferri (iron-free) (3)H-schizokinen to levels equivalent to those incorporated from the chelate form was noted in strain SK11, but strain ATCC 19213 showed only temperature-independent binding of low concentrations of deferri (3)H-schizokinen. These results indicate an initial temperature-independent binding of the ferric hydroxamate which is followed rapidly by temperature-dependent transport of the chelate into the cell and an enzyme catalyzed separation of iron from the chelate. The resulting deferri hydroxamate is discharged from the cell only when a characteristic intracellular concentration of the hydroxamate is exceeded, which happens in the schizokinen-requiring strain only at elevated concentrations of the chelate. This strain also appears to draw the deferri hydroxamate into the cell by a temperature-dependent mechanism. The aerobactin-producing organism Aerobacter aerogenes 62-1 also demonstrated rapid initial uptake and temperature-dependent discharge of (3)H-aerobactin during iron transport from (3)H-aerobactin-(59)Fe(3+), suggesting a similar ferric hydroxamate transport system in this organism. 相似文献
99.
It has been shown by surface potential measurements that lysine vasopressin and oxytocin may be bound by ionic surfaces to very varied extents. To dodecyl sulphate and phosphatidylserine monolayers the binding is very strong and is comparable to that for biological receptors such as those in toad bladder. For dioleyl phosphate and the carboxyl group of the polypeptide alamethicin, the binding is rather weaker while, for the zwitterionic lipids phosphatidylcholine and phosphatidylethanolamine, and for the erythrocyte surface, which contains two varieties of carboxylic acid group, no interaction seems to take place.In no system does the lysyl amino group of the vasopressin appear necessary for adsorption and, in the dodecyl sulphate monolayers, the interaction is strong even when the ionization of the terminal α-amino group is suppressed. 相似文献
100.
Summary Then-alkyl bromides with 6 to 10 carbons induce formation of vesicles of 5 to 100 m diameter from the small vesicles (0.1 m average diameter) produced by disruption of the discs from frog rod photoreceptors. Then-alkanes,n-alkyl iodides andn-alkyl chlorides are relatively ineffective. The formation of large vesicles is independent of calcium concentration and is distinguished from fusion processes previously reported by the large number of vesicles involved. The results reported here together with others suggest the occurrence of multiple fusion (and/or rupture-resealing) events between vesicles, induced by then-alkyl bromides. 相似文献