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1.
R W Chrisman S Mansy H J Peresie A Ranade T A Berg R S Tobias 《Bioinorganic chemistry》1977,7(3):245-266
Raman spectra have been obtained for dTMP and its complex with CH3Hg (II) in aqueous solution as a function of pH. Difference spectroscopy is employed to increase the sensitivity of the Raman technique. The binding reaction is essentially quantitative from pH 3 to 9, and the value of the equilibrium constant for CH3HgOH2+ + dThd in equilibrium CH3Hg(dThdH--1) + H30+ is estimated from intensity measurements to be 0.6 in reasonable agreement with an earlier value based upon uv spectrophotometric data. Binding is to N(3) with substitution of CH3Hg+ for the proton. A similar reaction occurs with 1-MeThy. Raman spectra for aqueous and crystalline 1-MeThy and for the complex CH3Hg(1-MeThyH--1) are reported. The spectrum of crystalline Hg(1-MeThyH--1)2, for which the crystal structure is known, also was obtained for comparison. Raman difference spectroscopy was used to confirm that CH3Hg (II) binds to N(3) of dTMP and N(1) of GMP at r = 0.2 (MeHg+: phosphate) ratios with mixtures of GMP + CMP + AMP + dTMP. In contrast, native calf thymus DNA does not appear to bind CH3Hg(II) at these sites at r = 0.15, although no significant amount of free CH3HgOH is present. With r = 0.3, extensive binding occurs both to the Thy and Gua bases. Raman difference spectroscopy is a valuable technique for studying the binding of ions and molecules to polynucleotides in moderately dilute aqueous solution. 相似文献
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3.
Sayali C. Ranade Sarfaraz Nawaz Arnab Chakrabarti Pierre Gressens Shyamala Mani 《Hormones and behavior》2013
"The goal of this study was to examine the effect of maternal iron deficiency on the developing hippocampus in order to define a developmental window for this effect, and to see whether iron deficiency causes changes in glucocorticoid levels. The study was carried out using pre-natal, post-natal, and pre + post-natal iron deficiency paradigm. Iron deficient pregnant dams and their pups displayed elevated corticosterone which, in turn, differentially affected glucocorticoid receptor (GR) expression in the CA1 and the dentate gyrus. Brain Derived Neurotrophic Factor (BDNF) was reduced in the hippocampi of pups following elevated corticosterone levels. Reduced neurogenesis at P7 was seen in pups born to iron deficient mothers, and these pups had reduced numbers of hippocampal pyramidal and granule cells as adults. Hippocampal subdivision volumes also were altered. The structural and molecular defects in the pups were correlated with radial arm maze performance; reference memory function was especially affected. Pups from dams that were iron deficient throughout pregnancy and lactation displayed the complete spectrum of defects, while pups from dams that were iron deficient only during pregnancy or during lactation displayed subsets of defects. These findings show that maternal iron deficiency is associated with altered levels of corticosterone and GR expression, and with spatial memory deficits in their pups." 相似文献
4.
Matthew A. Haemer Daksha Ranade Anna E. Barón Nancy F. Krebs 《Obesity (Silver Spring, Md.)》2013,21(5):1004-1012
Objective:
Preschool and minority children have not been well represented in obesity treatment studies. This analysis of clinical obesity treatment was carried out within a diverse population of children 2‐12 years to identify demographic characteristics associated with successful treatment.Design and Methods:
A medical record review captured BMI and demographics for children 2‐12 years who began treatment during a 42‐month period (n = 479). Associations of body mass index z‐score (BMI‐Z) change with child and family demographics were examined with logistic regression and time‐to‐event analysis.Results:
Treatment led to a mean BMI‐Z decrease of 0.18. Half of children with follow‐up (n = 273) exceeded the a priori cut‐off for successful treatment of ?0.1 BMI‐Z. Preschoolers and children of Spanish‐speakers were more likely to succeed, (Adjusted OR: 5.8 [95% CI: 2.7‐12.2] and 2.3 [95% CI: 1.1, 4.9]). The hazard ratio for treatment failure was 3.7 [95% CI: 2.1, 6.8] for children starting treatment at 6‐12 years compared to preschoolers, adjusted for other demographics.Conclusions:
This mode of treatment was more likely to succeed among children treated before school age and among children whose parents spoke only Spanish. Screening and treatment for obesity in preschoolers and Hispanic immigrant families deserve further prospective study.5.
Kayode K. Ojo Ranae M. Ranade Zhongsheng Zhang David M. Dranow Janette B. Myers Ryan Choi Steve Nakazawa Hewitt Thomas E. Edwards Douglas R. Davies Donald Lorimer Stephen M. Boyle Lynn K. Barrett Frederick S. Buckner Erkang Fan Wesley C. Van Voorhis 《PloS one》2016,11(8)
We investigated Brucella melitensis methionyl-tRNA-synthetase (BmMetRS) with molecular, structural and phenotypic methods to learn if BmMetRS is a promising target for brucellosis drug development. Recombinant BmMetRS was expressed, purified from wild type Brucella melitensis biovar Abortus 2308 strain ATCC/CRP #DD-156 and screened by a thermal melt assay against a focused library of one hundred previously classified methionyl-tRNA-synthetase inhibitors of the blood stage form of Trypanosoma brucei. Three compounds showed appreciable shift of denaturation temperature and were selected for further studies on inhibition of the recombinant enzyme activity and cell viability against wild type B. melitensis strain 16M. BmMetRS protein complexed with these three inhibitors resolved into three-dimensional crystal structures and was analyzed. All three selected methionyl-tRNA-synthetase compounds inhibit recombinant BmMetRS enzymatic functions in an aminoacylation assay at varying concentrations. Furthermore, growth inhibition of B. melitensis strain 16M by the compounds was shown. Inhibitor-BmMetRS crystal structure models were used to illustrate the molecular basis of the enzyme inhibition. Our current data suggests that BmMetRS is a promising target for brucellosis drug development. However, further studies are needed to optimize lead compound potency, efficacy and safety as well as determine the pharmacokinetics, optimal dosage, and duration for effective treatment. 相似文献
6.
Inactivation of Salmonella typhi by high levels of volatile fatty acids during anaerobic digestion 总被引:1,自引:0,他引:1
Survival of Salmonella typhi was investigated in an anaerobic digester for cattle dung with volatile fatty acid (VFA) levels of 5000 mg l(-1) and pH 6.0. The organism was added to the digester only once in the first experiment and daily in the other. Survival was monitored on alternate days. In the single dose experiment, the counts of Salm. typhi declined rapidly and the pathogen was completely eliminated within 12 d in the experimental digester (VFA ca 5000 mg l(-1) and pH 6.0), whereas 26 d were required in the control digester (VFA ca 100 mg l(-1) and pH 6.8). T90 values for the experimental and control digesters were 2.44 d and 4.80 d, respectively. In the daily dose experiment, a four log reduction in the pathogen count was observed in the experimental digester, but only a two log reduction in the control digester at the end of the experimental period. The mean T90 values for the experimental and the control digester were 4.22 d and 18.63 d, respectively. In both the experiments, statistical analysis of the data showed significant differences in the survival pattern of Salm. typhi in the two digesters. 相似文献
7.
When human cells are stressed during G2, they are delayed from entering mitosis via a checkpoint mediated by the p38 kinase, and this delay can be modeled by the selective activation of p38 with anisomycin. Here, we report, on the basis of live-cell studies, that 75 nM anisomycin transiently (1 hr) activates p38 which, in turn, rapidly and completely blocks entry into mitosis for at least 4 hr in all primary, telomerase- or spontaneously immortalized (p53+ and pRB+) human cells. However, the same treatment does not delay entry into mitosis in cancer cells, or the delay in entering mitosis is shortened, even though it induces a similar transient and comparable (or stronger) activation of p38. Because the primary substrate of p38, the MK2 kinase, is also transiently (1-2 hr) activated by anisomycin in both normal and cancer cells, checkpoint disruption in transformed cells occurs downstream of MK2. Finally, observations on isogenic lines reveal that the duration of the stress checkpoint is shortened in cells lacking both p53 and pRb and that the constitutive expression of an active H-Ras oncogene in these cells further attenuates the checkpoint via an ERK1/2-dependent manner. Thus, transformation leads to attenuation of the p38-mediated stress checkpoint. This outcome is likely selected for during transformation because it confers the ability to outgrow normal cells under stressful in vitro (culture) or in vivo (tumor) environments. Our data caution against using cancer cells to study how p38 produces a G2 arrest. 相似文献
8.
Thakker C Burhanpurwala Z Rastogi G Shouche Y Ranade D 《Indian journal of experimental biology》2006,44(2):142-150
In the present study, isolation of anaerobic bacteria from 24 different eco-niches was carried out. A total number of 300 bacterial isolates, including 230 obligate and 70 facultative anaerobes were obtained using anaerobic techniques. All the isolates were initially screened for succinic acid production by Fluorescein test and TLC method. During screening, 10 isolates found to produce succinic acid were further examined by HPLC and then finally confirmed for succinic acid by LC-MS analysis. Amongst 10 isolates, isolate SAP, a facultative anaerobe isolated from buffalo rumen fluid, showed maximum yield of 2.1 g/l of succinic acid from 10 g of glucose in 24 hr under anaerobic condition. This isolate was identified as Klebsiella pneumoniae strain SAP by 16S rDNA sequence and signature sequence analysis. Mouse lethality test for the strain SAP showed LD50 value of 3.3 x 10(8) CFU/ml, which shows non-virulent nature of the strain. This strain may become a candidate strain for succinic acid production because of its osmotolerant nature and higher succinate:acetate ratio. 相似文献
9.
Genome-wide analysis of p63 binding sites identifies AP-2 factors as co-regulators of epidermal differentiation 总被引:1,自引:0,他引:1
10.
Significant advances have been made in our understanding of heat shock protein 90 (Hsp90) in terms of its structure, biochemical characteristics, post-translational modifications, interactomes, regulation and functions. In addition to yeast as a model several new systems have now been examined including flies, worms, plants as well as mammalian cells. This review discusses themes emerging out of studies reported on Hsp90 from infectious disease causing protozoa. A common theme of sensing and responding to host cell microenvironment emerges out of analysis of Hsp90 in Malaria, Trypanosmiasis as well as Leishmaniasis. In addition to their functional roles, the potential of Hsp90 from these infectious disease causing organisms to serve as drug targets and the current status of this drug development endeavor are discussed. Finally, a unique and the only known example of a split Hsp90 gene from another disease causing protozoan Giardia lamblia and its evolutionary significance are discussed. Clearly studies on Hsp90 from protozoan parasites promise to reveal important new paradigms in Hsp90 biology while exploring its potential as an anti-infective drug target. This article is part of a Special Issue entitled: Heat Shock Protein 90 (HSP90). 相似文献