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排序方式: 共有105条查询结果,搜索用时 296 毫秒
91.
92.
Juan Carlos Q. Velez Michael G. Janech Megan P. Hicks Thomas A. Morinelli Jessalyn Rodgers Sally E. Self John M. Arthur Wayne R. Fitzgibbon 《PloS one》2014,9(10)
Unopposed angiotensin (Ang) II-mediated cellular effects may lead to progressive glomerulosclerosis. While Ang-II can be locally generated in the kidneys, we previously showed that glomerular podocytes primarily convert Ang-I, the precursor of Ang-II, to Ang-(1-7) and Ang-(2-10), peptides that have been independently implicated in biological actions opposing those of Ang-II. Therefore, we hypothesized that Ang-(1-7) and Ang-(2-10) could be renoprotective in the fawn-hooded hypertensive rat, a model of focal segmental glomerulosclerosis. We evaluated the ability of 8–12 week-long intravenous administration of either Ang-(1-7) or Ang-(2-10) (100–400 ng/kg/min) to reduce glomerular injury in uni-nephrectomized fawn-hooded hypertensive rats, early or late in the disease. Vehicle-treated rats developed hypertension and lesions of focal segmental glomerulosclerosis. No reduction in glomerular damage was observed, as measured by either 24-hour urinary protein excretion or histological examination of glomerulosclerosis, upon Ang-(1-7) or Ang-(2-10) administration, regardless of peptide dose or disease stage. On the contrary, when given at 400 ng/kg/min, both peptides induced a further increase in systolic blood pressure. Content of Ang peptides was measured by parallel reaction monitoring in kidneys harvested at sacrifice. Exogenous administration of Ang-(1-7) and Ang-(2-10) did not lead to a significant increase in their corresponding intrarenal levels. However, the relative abundance of Ang-(1-7) with respect to Ang-II was increased in kidney homogenates of Ang-(1-7)-treated rats. We conclude that chronic intravenous administration of Ang-(1-7) or Ang-(2-10) does not ameliorate glomerular damage in a rat model of focal segmental glomerulosclerosis and may induce a further rise in blood pressure, potentially aggravating glomerular injury. 相似文献
93.
Pseudomonas sp. strain PG2982 has the ability to use the phosphonate herbicide, glyphosate, as a sole phosphorus source (J. K. Moore, H. D. Braymer, and A. D. Larson, Appl. Environ. Microbiol. 46:316-320, 1983). Glyphosate uptake is maximal in the late log phase of growth and is induced by phosphate starvation. Uptake is inhibited by phosphate and arsenate, but not by the amino acids glycine and sarcosine. The Km and Vmax for glyphosate uptake were calculated to be 23 microM and 0.97 nmol/mg (dry weight) per min, respectively. A phosphate transport system with a broad substrate specificity may be responsible for glyphosate uptake. 相似文献
94.
Joanne M. Hildebrand Bernice Lo Sara Tomei Valentina Mattei Samuel N. Young Cheree Fitzgibbon James M. Murphy Abeer Fadda 《Cell death & disease》2021,12(4)
Maturity-onset diabetes of the young, MODY, is an autosomal dominant disease with incomplete penetrance. In a family with multiple generations of diabetes and several early onset diabetic siblings, we found the previously reported P33T PDX1 damaging mutation. Interestingly, this substitution was also present in a healthy sibling. In contrast, a second very rare heterozygous damaging mutation in the necroptosis terminal effector, MLKL, was found exclusively in the diabetic family members. Aberrant cell death by necroptosis is a cause of inflammatory diseases and has been widely implicated in human pathologies, but has not yet been attributed functions in diabetes. Here, we report that the MLKL substitution observed in diabetic patients, G316D, results in diminished phosphorylation by its upstream activator, the RIPK3 kinase, and no capacity to reconstitute necroptosis in two distinct MLKL−/− human cell lines. This MLKL mutation may act as a modifier to the P33T PDX1 mutation, and points to a potential role of impairment of necroptosis in diabetes. Our findings highlight the importance of family studies in unraveling MODY’s incomplete penetrance, and provide further support for the involvement of dysregulated necroptosis in human disease.Subject terms: Necroptosis, Diabetes 相似文献
95.
The lesser pouched rat, Beamys hindei Thomas 1909, is one of Africa's rarest and least known rodents, recorded only from a few localities in Kenya and Tanzania. The results of this study show that B. hindei is more widely distributed than previously thought and occurs at high densities in suitable habitat. It breeds throughout the year, but maintains relatively constant population densities as recruitment rates are low. On account of its ability to cache food, it is well adapted to seasonally dry forests where food is in short supply for part of the year. The need for suitable soil in which to construct its burrows and dense vegetation cover may partly account for its patchy distribution. Morphological data collected during this study provide no evidence for separating B. hindei from B. major and suggest that the differences previously recorded between the two forms may be actually due to clinal variation in size from north to south. 相似文献
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Montalescot G.; Kreil E.; Lynch K.; Greene E. M.; Torres A.; Carvalho A.; Fitzgibbon C.; Robinson D. R.; Lowenstein E.; Zapol W. M. 《Journal of applied physiology》1989,66(5):2344-2350
In six awake sheep the control heparin-protamine reaction was associated with a 150-fold rise in arterial plasma thromboxane B2 (TxB2) levels, a 4.5-fold increase in pulmonary vascular resistance, a 20% decrease in cardiac output, a 30% decrease in arterial PO2, and a 30% reduction in arterial white blood cell concentrations. Depletion of 99% of circulating platelets by antibodies did not prevent either acute and severe pulmonary hypertension or increased plasma TxB2 levels induced by heparin-protamine administration. We produced sheep platelet aggregation in vitro with bovine thrombin and measured marked TxB2 release (36.3 +/- 16.3 ng/10(9) platelets). In contrast, neither heparin, protamine, nor heparin-protamine complexes over a 10,000-fold range of concentrations induced platelet aggregation and release of thromboxane in vitro. Therefore sheep platelets are not the source of thromboxane production associated with acute pulmonary hypertension during the heparin-protamine reaction, and other cells must produce the thromboxane. 相似文献
99.
Aims: To compare the inactivation rate of Venezuelan equine encephalomyelitis (VEE) virus in liquids to that of Sindbis virus (SV, another alphavirus) and to a bacteriophage (MS2) generally used as a viral simulant in the development of countermeasures in biodefense. Methods and Results: Viruses were inoculated into liquids and viral titres were determined at various times postinoculation. The viruses were stable in distilled-deionized (dd) water at 4°C during the 21 days of the study. The inactivation rates of VEE and SV in dd water at 21 and 30°C were very similar (between 0·12 and 0·14 log10 per day), while MS2 was three-fold slower. In tap water (chlorine content between 4 and 5 ppm) at 21°C, VEE and SV were inactivated at twice the rate measured in dd water. Conclusions: The inactivation rates of VEE and SV were similar to each other and faster than MS2 in all liquids tested. Significance and Impact of the Study: VEE is likely to remain viable for many days after release into water, snow, or even chlorinated tap water. SV can be used to estimate the persistence of VEE in liquids, but using MS2 as a simulant would overestimate of the stability of VEE. 相似文献
100.
Epidermal growth factor-induced precocious incisor eruption is associated with decreased tooth size 总被引:2,自引:1,他引:1
Epidermal growth factor (EGF) causes precocious eruption of incisors in vivo and is mitogenic for tooth-derived cells in vitro. These two observations lead to the hypothesis that the EGF-induced precocious eruption is the result of an increase in the size of the incisor. To test this hypothesis, neonatal mice were injected daily with various doses of EGF and, seven days after birth, were perfused with fixative. EGF causes a retardation of overall growth (as measured by body weight) and a dose-dependent thickening of the epidermis. The incisors were examined in midsagittal histological sections and in X-ray microradiographs. Contrary to our expectations, EGF causes a dose-dependent decrease in the size of the incisors. This result suggests that the stimulation of the growth of odontogenic cells seen in tissue culture is not part of the physiological response to EGF in vivo and that EGF-induced precocious eruption of incisors is not due to an increase in the growth rate of the tooth. 相似文献