全文获取类型
收费全文 | 65篇 |
免费 | 6篇 |
专业分类
71篇 |
出版年
2017年 | 2篇 |
2016年 | 2篇 |
2014年 | 3篇 |
2013年 | 8篇 |
2012年 | 2篇 |
2009年 | 1篇 |
2008年 | 2篇 |
2006年 | 1篇 |
2005年 | 2篇 |
2003年 | 2篇 |
2002年 | 3篇 |
2001年 | 5篇 |
2000年 | 1篇 |
1999年 | 1篇 |
1998年 | 5篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1992年 | 3篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有71条查询结果,搜索用时 15 毫秒
41.
Phylogenetic utility of elongation factor-1 alpha in noctuoidea (Insecta: Lepidoptera): the limits of synonymous substitution 总被引:1,自引:1,他引:1
Mitchell A; Cho S; Regier JC; Mitter C; Poole RW; Matthews M 《Molecular biology and evolution》1997,14(4):381-390
To test its phylogenetic utility, nucleotide sequence variation in a
1,240-bp fragment of the elongation factor-1 alpha (EF-1 alpha) gene was
examined in 49 moth species representing the major groups of the
superfamily Noctuoidea. Both parsimony and distance analyses supported the
monophyly of nearly all groups for which there are clear morphological
synapomorphies. Clades of subfamily rank and lower, probably mid-Tertiary
and younger, were strongly supported. The third codon position contains 88%
of variable sites, and approaches saturation at approximately 20% sequence
divergence, possibly due to among-site rate heterogeneity and composition
bias; higher divergences occur only in association with shifts in
composition. Surprisingly, the few nonsynonymous changes appear no more
phylogenetically reliable than synonymous changes. Signal strength for
basal divergences is weak and fails to improve with character weighting;
thus, dense taxon sampling is probably needed for strong inference from
EF-1 alpha regarding deeper splits in Noctuoidea (probably early Tertiary).
EF-1 alpha synonymous changes show promise for phylogeny reconstruction
within Noctuidae and other groups of Tertiary age.
相似文献
42.
Diluk RW Kannangara Sheena N Ramasamy Praveen L Indraratna Sophie L Stocker Garry G Graham Graham Jones Ian Portek Kenneth M Williams Richard O Day 《Arthritis research & therapy》2012,14(4):R189
Introduction
Hyperuricemia is the greatest risk factor for gout and is caused by an overproduction and/or inefficient renal clearance of urate. The fractional renal clearance of urate (FCU, renal clearance of urate/renal clearance of creatinine) has been proposed as a tool to identify subjects who manifest inefficient clearance of urate. The aim of the present studies was to validate the measurement of FCU by using spot-urine samples as a reliable indicator of the efficiency of the kidney to remove urate and to explore its distribution in healthy subjects and gouty patients.Methods
Timed (spot, 2-hour, 4-hour, 6-hour, 12-hour, and 24-hour) urine collections were used to derive FCU in 12 healthy subjects. FCUs from spot-urine samples were then determined in 13 healthy subjects twice a day, repeated on 3 nonconsecutive days. The effect of allopurinol, probenecid, and the combination on FCU was explored in 11 healthy subjects. FCU was determined in 36 patients with gout being treated with allopurinol. The distribution of FCU was examined in 118 healthy subjects and compared with that from the 36 patients with gout.Results
No substantive or statistically significant differences were observed between the FCUs derived from spot and 24-hour urine collections. Coefficients of variation (CVs) were both 28%. No significant variation in the spot FCU was obtained either within or between days, with mean intrasubject CV of 16.4%. FCU increased with probenecid (P < 0.05), whereas allopurinol did not change the FCU in healthy or gouty subjects. FCUs of patients with gout were lower than the FCUs of healthy subjects (4.8% versus 6.9%; P < 0.0001).Conclusions
The present studies indicate that the spot-FCU is a convenient, valid, and reliable indicator of the efficiency of the kidney in removing urate from the blood and thus from tissues. Spot-FCU determinations may provide useful correlates in studies investigating molecular mechanisms underpinning the observed range of efficiencies of the kidneys in clearing urate from the blood.Trial Registration
ACTRN12611000743965 相似文献43.
Three of the five disulfide bonds in the glycoprotein hormone alpha-subunit (GPH-alpha) form a cystine knot motif that stabilizes a three-loop antiparallel structure. Previously, we described a mutant (alpha(k)) that contained only the three knot disulfide bonds and demonstrated that the cystine knot was necessary and sufficient for efficient GPH-alpha folding and secretion. In this study, we used alpha(k) as a model to study the intracellular GPH-alpha folding pathway. Cystine knot formation proceeded through a 1-disulfide intermediate that contained the 28-82 disulfide bond. Formation of disulfide bond 10-60, then disulfide bond 32-84, followed the formation of 28-82. Whether the two non-cystine knot bonds 7-31 and 59-87 could form independent of the knot was also tested. Disulfide bond 7-31 formed rapidly, whereas 59-87 did not form when all cysteine residues of the cystine knot were converted to alanine, suggesting that 7-31 forms early in the folding pathway and that 59-87 forms during or after cystine knot formation. Finally, loop 2 of GPH-alpha has been shown to be very flexible, suggesting that loop 2 does not actively drive GPH-alpha folding. To test this, we replaced residues 36-55 in the flexible loop 2 with an artificially flexible glycine chain. Consistent with our hypothesis, folding and secretion were unaffected when loop 2 was replaced with the glycine chain. Based on these findings, we describe a model for the intracellular folding pathway of GPH-alpha and discuss how these findings may provide insight into the folding mechanisms of other cystine knot-containing proteins. 相似文献
44.
Background
As the use of microarray technology becomes more prevalent it is not unusual to find several laboratories employing the same microarray technology to identify genes related to the same condition in the same species. Although the experimental specifics are similar, typically a different list of statistically significant genes result from each data analysis. 相似文献45.
Human responses to propionic acid. I. Quantification of within- and between-participant variation in perception by normosmics and anosmics 总被引:4,自引:3,他引:1
The objective of this study was to fully characterize normosmic perception
of stimuli expected to cause widely varying degrees of olfactory and nasal
trigeminal stimulation and to directly evaluate the possible role of
olfactory nerve stimulation in nasal irritation sensitivity. During each of
four identical test sessions, four anosmic and 31 normosmic participants
were presented with a range of concentrations extending from peri-threshold
for normosmics to supra- threshold for anosmics. For each session, odor (O)
and nasal irritation (NI) sensitivities were summarized in terms of the
concentrations required to produce four sensation levels ('iso-response'
concentrations). Within-participant variation in these iso-response
concentrations was < 10-fold for 95% of normosmics, for both O and NI.
For O but not NI, these apparent fluctuations in sensitivity were largely
accounted for by the uncertainty surrounding the iso-response
concentrations calculated for each session. Anosmics exhibited minimal
within- and between-participant variation in NI and required, for all but
the highest perceptual level, a higher concentration than almost all
normosmics. Between-participant variation, expressed in terms of 90%
confidence interval widths, was approximately 0.5 log units for both O and
NI for the highest perceptual level, but increased to approximately 0.8 and
1.8 log units, respectively, for the lowest (peri- threshold) level. Our
findings suggest that: (i) most apparent variation over time in O
sensitivity is actually a reflection of the uncertainty surrounding
estimates of sensitivity obtained for each session; (ii) within- and
between-participant variation in O sensitivity is far less than is commonly
reported; and (iii) low to moderate levels of NI in normosmics are the
result of relatively weak trigeminal stimulation combined with much greater
olfactory activation.
相似文献
46.
The IgG1hybridoma antibody, 91.9H, was originally raised against sulfated
mucins isolated from normal human colonic mucosa. Previous studies have
shown that the 91.9H antigen is expressed on normal colonic epithelial
cells and the sulfomucins that they produce, but not in the normal small
intestine and stomach. Tissue-specific changes occur in 91.9H antigen
expression in disease: the antigen diminishes in colonic carcinomas,
whereas in regions of gastric mucosa showing intestinal metaplasia and in
gastric carcinomas, the antigen is expressed as a "neo-antigen." This
report is concerned with elucidation, by the neoglycolipid technology, of
the determinant recognized by antibody 91.9H using sulfated and sialyl
oligosaccharides of Lewisa(Lea) and Lextypes, and analogs that lack
sulfate, sialic acid, or fucose. Binding experiments with the lipid-linked
oligosaccharides immobilized on chromatograms or on microwells, and
inhibition of binding experiments with free oligosaccharides based on di-,
tri- and tetrasaccharide backbones, show that the 91.9H antigenic
determinant is based on a trisaccharide backbone, and consists of the
3'-sulfated Leatetrasaccharide sequence, which is a potent ligand for the
E- and L-selectins. The antibody gives a relatively low signal with the
3'-sulfated non-fucosylated backbone, and has no detectable cross- reaction
with the 3'-sulfated Lexisomer, nor with sialyl-Leaand - Lexanalogues.
Antibody 91.9H is a valuable addition, therefore, to the repertoire of
reagents for mapping details of the distribution, and determining the
relative importance of sulfated and sialyl oligosaccharides as ligands for
the selectins, in normal and pathological epithelia and endothelia.
相似文献
47.
A phosphoprotein kinase (EC 2.7.1.37) KIVb, from rat liver nuclei, was purified 75-fold by phosphocellulose chromatography and gel filtration on Sephadex G-200. The enzyme, which has an apparent molecular weight of 55 000, phosphorylates casein and chromatin-bound nonhistone proteins more readily than histones or ribosomal proteins. It exhibits an absolute requirement for divalent cation with optimum activity at 15--20 mM Mg2+. Maximal kinase activity is achieved at 100 mM NaCl. The pH vs. activity curve is biphasic with optima at pH 6.5 and pH 8.0. The Km value for casein is 280 mug/ml and the Km for ATP is 6-10(-6) M. Kinase KIVb phosphorylates numerous nonhistone nuclear proteins as shown by electrophoretic analysis. The addition of kinase KIVb to reaction mixtures containing nonhistone proteins results in the phosphorylation of a spectrum of polypeptides similar to those that are phosphorylated by endogenous nuclear kinases. Nonhistone proteins bound to chromatin appear to be better substrates for KIVb than nonhistones dissociated from chromatin. A comparison of nuclear phosphoproteins phosphorylated either in the intact animal or in vitro (by the addition of kinase KIVb) indicates some differences and some similarities in the patterns of phosphorylation. 相似文献
48.
The role of cAMP in the regulation of nuclear protein kinase activity was investigated. Acidic nuclear proteins prepared from rat liver nuclei were separated by phosphocellulose chromatography into four peaks of protein kinase activity and two peaks of cAMP-binding activity. A fraction which bound cAMP also inhibited the most active nuclear protein kinase, K IV, and the inhibition was diminished in the presence of 5 μM cAMP. Further support for the regulation of nuclear kinases by cAMP was obtained using a regulatory subunit prepared from rabbit muscle protein kinase. The muscle regulatory subunit markedly inhibited liver nuclear kinase activities. The addition of cAMP partially restored the activities. 相似文献
49.
J S Beebe K Mountjoy R F Krzesicki F Perini R W Ruddon 《The Journal of biological chemistry》1990,265(1):312-317
The malignant trophoblastic cell line JAR was used as a model system to study protein folding in intact cells. We have used this model previously to identify conformational intermediates in the production of an assembly-competent form of the human chorionic gonadotropin beta subunit (Ruddon, R. W., Krzesicki, R. F., Norton, S. E., Beebe, J. S., Peters, B. P., and Perini, F. (1987) J. Biol. Chem. 262, 12533-12540). The earliest biosynthetic precursor of the human chorionic gonadotropin beta subunit detectable in JAR cells pulse labeled for 2 min is p beta 1, a form that lacks half of the six intrachain disulfide bonds observed in the fully processed dimer form of beta and that does not combine with the alpha subunit. p beta 1 is rapidly (t1/2 approximately 4 min) converted into p beta 2, which has a full complement of intrachain disulfide bonds and does combine with the alpha subunit. In this study, we have identified the three late forming disulfide bonds involved in the transition of p beta 1 into the assembly-compete form, p beta 2. The last three disulfide bonds to form are those between cysteines 9 and 90, 23 and 72, and 93 and 100. These were identified in JAR cell lysates that had been pulse labeled with [35S]cysteine for 2 or 5 min followed by trapping of the cysteine thiols with iodoacetic acid before immunopurification of the beta subunit forms. Immunopurified p beta 1 was treated with trypsin under nonreducing conditions to liberate [35S]cysteine-containing peptides from the disulfide-linked beta core polypeptide. These tryptic peptides were then separated by high performance liquid chromatography and sequenced to determine the location of the carboxymethyl-[35S]cysteine residues. The three late forming disulfide bonds are most likely the ones involved in stabilizing the conformation of the beta subunit that is required for combination with alpha to form the biologically functional alpha beta heterodimer. 相似文献
50.