全文获取类型
收费全文 | 266篇 |
免费 | 19篇 |
出版年
2023年 | 3篇 |
2022年 | 1篇 |
2021年 | 3篇 |
2020年 | 1篇 |
2019年 | 3篇 |
2018年 | 4篇 |
2017年 | 4篇 |
2016年 | 7篇 |
2015年 | 10篇 |
2014年 | 10篇 |
2013年 | 16篇 |
2012年 | 24篇 |
2011年 | 14篇 |
2010年 | 9篇 |
2009年 | 9篇 |
2008年 | 14篇 |
2007年 | 14篇 |
2006年 | 12篇 |
2005年 | 16篇 |
2004年 | 21篇 |
2003年 | 21篇 |
2002年 | 17篇 |
2001年 | 8篇 |
2000年 | 4篇 |
1999年 | 5篇 |
1998年 | 3篇 |
1997年 | 6篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 3篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1977年 | 1篇 |
1976年 | 3篇 |
1964年 | 1篇 |
排序方式: 共有285条查询结果,搜索用时 31 毫秒
1.
Based on its proven anabolic effects on bone in osteoporosis patients, recombinant parathyroid hormone (PTH1-34) has been evaluated as a potential therapy for skeletal repair. In animals, the effect of PTH1-34 has been investigated in various skeletal repair models such as fractures, allografting, spinal arthrodesis and distraction
osteogenesis. These studies have demonstrated that intermittent PTH1-34 treatment enhances and accelerates the skeletal repair process via a number of mechanisms, which include effects on mesenchymal
stem cells, angiogenesis, chondrogenesis, bone formation and resorption. Furthermore, PTH1-34 has been shown to enhance bone repair in challenged animal models of aging, inflammatory arthritis and glucocorticoid-induced
bone loss. This pre-clinical success has led to off-label clinical use and a number of case reports documenting PTH1-34 treatment of delayed-unions and non-unions have been published. Although a recently completed phase 2 clinical trial of PTH1-34 treatment of patients with radius fracture has failed to achieve its primary outcome, largely because of effective healing
in the placebo group, several secondary outcomes are statistically significant, highlighting important issues concerning the
appropriate patient population for PTH1-34 therapy in skeletal repair. Here, we review our current knowledge of the effects of PTH1-34 therapy for bone healing, enumerate several critical unresolved issues (e.g., appropriate dosing regimen and indications)
and discuss the long-term potential of this drug as an adjuvant for endogenous tissue engineering. 相似文献
2.
The addition of antimycin A during the logarithmic phase of growth of heterotrophic Euglena gracilis cultures (in lactate or glucose medium) was immediately followed by decreased respiration and a cessation of grwoth. Induced cyanideresistent respiration appeared 5 h after the addition of the inhibitor then the cells started to grow again and could be cultured in the presence of antimycin A. Thus the cells exhibited a cyanide-and antimycin-resistant respiration which was, in addition, sensitive to salicylhydroxamic acid and propylgallate. Antimycin-adapted Euglena and control cells were compared for their biomass production and protein synthesis. The difference in growth yield between control and antimycin-adapted cells was not as high as would be expected if only the first phosphorylation site of the normal respiratory chain was active in the presence of antimycin A. Furthermore, the ability to incorporate labelled valine into proteins, under resting-cell conditions, was not changed. Strong correlations were established between the effects of respiratory effectors on O2 consumption and valine incorporation. These results suggest that sufficient energy for protein synthesis and growth is provided by the operation of the cyanide-resistant respiratory pathway in antimycin-adapted Euglena.Abbreviations DNP
dinitrophenol
- PG
propylgallate
- SHAM
salicylhydroxamic acid 相似文献
3.
Tom Strachan Alan B. Dodge David Smillie Philip A. Dyer Regis Sodoyer Bertrand R. Jordan Rodney Harris 《Immunogenetics》1986,23(2):115-120
Analysis of available nucleotide sequence data for class I HLA genes has established that the seventh intron is one of the gene regions which expresses the highest degree of locus specificity (the percentage sequence divergence between nonallelic genes minus the percentage sequence divergence between allelic genes). We have subcloned short DNA sequences including this region from the HLA-Cw3 gene. Two clones, pC250 and pC800, were tested by hybridizing them at high stringency to a panel of clones containing class I HLA genes. Under conditions permitting a strong hybridization signal with a C-locus gene, pC800 also expressed a weak but significant hybridization to other class I genes, while pC250 appeared to hybridize exclusively to the C-locus gene. Hybridization of the pC250 probe at high stringency to Hind III-digested genomic DNA from a panel of unrelated individuals and homozygous typing cell lines revealed a single band in all cases. However, equivalent hybridization against Eco RI-digested DNA revealed two hybridization bands, one at 7.9 kb which correlated with the serologically defined Cw5 and Cw8 alleles, and one at 7.6 kb which correlated with the Cw1, Cw2, Cw3, Cw4, Cw6, and Cw7 alleles. 相似文献
4.
E. Jay DeRocher Francoise Quigley Regis Mache Hans J. Bohnert 《Molecular genetics and genomics : MGG》1993,239(3):450-462
The nucleotide sequences of the entire gene family, comprising six genes, that encodes the Rubisco small subunit (rbcS) multigene family in Mesembryanthemum crystallinum (common ice plant), were determined. Five of the genes are arranged in a tandem array spanning 20 kb, while the sixth gene is not closely linked to this array. The mature small subunit coding regions are highly conserved and encode four distinct polypeptides of equal lengths with up to five amino acid differences distinguishing individual genes. The transit peptide coding regions are more divergent in both amino acid sequence and length, encoding five distinct peptide sequences that range from 55 to 61 amino acids in length. Each of the genes has two introns located at conserved sites within the mature peptide-coding regions. The first introns are diverse in sequence and length ranging from 122 by to 1092 bp. Five of the six second introns are highly conserved in sequence and length. Two genes, rbcS-4 and rbcS-5, are identical at the nucleotide level starting from 121 by upstream of the ATG initiation codon to 9 by downstream of the stop codon including the sequences of both introns, indicating recent gene duplication and/or gene conversion. Functionally important regulatory elements identified in rbcS promoters of other species are absent from the upstream regions of all but one of the ice plant rbcS genes. Relative expression levels were determined for the rbcS genes and indicate that they are differentially expressed in leaves. 相似文献
5.
Regis Vanderesse Laurent Thevenet Michel Marraud Nicole Boggetto Michele Reboud Catherine Corbier 《Journal of peptide science》2003,9(5):282-299
The aminoxy acids NH2-O-C(alpha)HR-CO2H are much more easily obtained in the enantiomerically pure form than the analogous hydrazino acids NH2-NH-C(alpha)HR-CO2H, and it has been shown that the isosteric amidoxy psi[CO-NH-O] and hydrazide psi[CO-NH-NH] amide surrogates Induce two quite similar gamma-like folded structures. An aminoxy acid can also be N-coupled to a peptide aldehyde to give the aldoxime psi[CH = N-O] link or to a peptide ketone to form the ketoxime psi[CR= N-O] link. The former can be further reduced into the hydroxylamine psi[CH2-NH-O] link which gives rise to reduced amidoxy peptides. The structural properties Induced by these amide surrogates were studied, using IR and NMR spectroscopy, paying particular attention to the Z/E-isomerism of the oxime link. In order to investigate their inhibitory potency, the three amide surrogates were introduced in the Pro3-Val4 and Val4-Ala5 position of Z-Ala1-Ala2-Pro3-Val4-Ala5-Ala6-NHiPr, a substrate which is cleaved in the Val4-Ala5 position by human leukocyte elastase (HLE). The [Val4psi[CO-NH-O]Ala5] analogue was still a substrate, while the [Pro3psi[CO-NH-O]Val4] and [Val4psi[CH = N-O]Ala5] pseudopeptides acted as HLE competitive inhibitors. 相似文献
6.
Modeling of adaptations to physical training by using a recursive least squares algorithm 总被引:3,自引:0,他引:3
Busso Thierry; Denis Christian; Bonnefoy Regis; Geyssant Andre; Lacour Jean-Rene 《Journal of applied physiology》1997,82(5):1685-1693
Busso, Thierry, Christian Denis, Régis Bonnefoy,André Geyssant, and Jean-René Lacour. Modeling ofadaptations to physical training by using a recursive least squaresalgorithm. J. Appl. Physiol. 82(5):1685-1693, 1997.The present study assesses the usefulnessof a systems model with time-varying parameters for describing theresponses of physical performance to training. Data for two subjectswho undertook a 14-wk training on a cycle ergometer were used to testthe proposed model, and the results were compared with a model withtime-invariant parameters. Two 4-wk periods of intensive training wereseparated by a 2-wk period of reduced training and followed by a 4-wkperiod of reduced training. The systems input ascribed to the trainingdoses was made up of interval exercises and computed in arbitraryunits. The systems output was evaluated one to five times per week byusing the endurance time at a constant workload. The time-invariantparameters were fitted from actual performances by using the leastsquares method. The time-varying parameters were fitted by using arecursive least squares algorithm. The coefficients of determinationr2 were 0.875 and0.879 for the two subjects using the time-varying model, higher thanthe values of 0.682 and 0.666, respectively, obtained with thetime-invariant model. The variations over time in the model parametersresulting from the expected reduction in the residuals appearedgenerally to account for changes in responses to training. Such a modelwould be useful for investigating the underlying mechanisms ofadaptation and fatigue. 相似文献
7.
Dense-core granules represent an adaptation of specialized secretory cell to facilitate stimulus-regulated release of stored proteins. Such granules are a prominent feature of mammalian neuroendocrine and exocrine cells and are also well developed in the ciliates. In Tet-rahymena thermophila, the ability to generate mutants in dense-core granule biosynthesis and fusion presents a versatile system for dissecting steps in regulated exocytosis. We have previously shown that defective granules in such mutants could be characterized by several biochemical criteria, including buoyant density, which increases during maturation, and the degree of proteolytic processing of the content precursors. We have now used indirect immunofluorescence, taking advantage of a monoclonal antibody directed against a granule protein, to visualize the morphology and distribution of both granules and putative granule intermediates in mutant and wild-type cells. The results are consistent with the biochemical analysis and extend our characterization of the mutants, allowing us to distinguish four classes. In addition, the assay represents a powerful technique for diagnosis of new mutants. © 1992 Wiley-Liss, Inc. 相似文献
8.
Brief exposure to the protein neurotoxin, β-bungarotoxin, is known to disrupt neuromuscular transmission irreversibly by blocking the release of transmitter from the nerve terminal. This neurotoxin also has a phospholipase A2 activity, although phospholipases in general are not very toxic. To determine if the toxicity of this molecule might result from specific binding to neural tissue, we have looked for high affinity, saturable binding using 125I-labeled toxin. At low membrane protein concentration 125I-labeled toxin binding was directly proportional to the amount of membrane; at fixed membrane concentration 125I-labeled toxin showed saturable binding. It was unlikely that iodination markedly changed the toxin's properties since the iodinated toxin had a comparable binding affinity to that of native toxin as judged by competition experiments. Comparison of toxin binding to brain, liver and red blood cell membranes showed that all had high affinity binding sites with dissociation constants between one and two nanomolar. This is comparable to the concentrations previously shown to inhibit mitochondrial function. However, the density of these sites showed marked variation such that the density of sites was 13.0 pmol/mg protein for a brain membrane preparation, 2.4 pmol/mg for liver and 0.25 pmol/mg for red blood cell membranes.In earlier work we had shown that calcium uptake by brain mitochondria is inhibited at much lower toxin concentrations than is liver mitochondrial uptake. Both liver and brain mitochondria bind toxin specifically, but the density of 125I-labeled toxin binding sites on brain mitochondrial prepartions () exceeded by a factor of ten the density on liver mitochondrial preparations (). It is also shown that the labeled toxin does not cross synaptosomal membranes, suggesting that mitochondria may not be the site of action of the toxin in vivo. We conclude the β-bungarotoxin is an enzyme which can bind specifically with high affinity to cell membranes. 相似文献
9.
Ana Paula de Araújo Maria Alice Varjal de Melo-Santos Sidney de Oliveira Carlos Eugênia Maria Mariz Maranho Rios Lêda Regis 《Biological Control》2007,41(3):339-347
The larvicidal activity of an experimental formulation of Bacillus thuringiensis israelensis (Bti) against Aedes aegypti larvae was evaluated under laboratory and simulated field conditions (SFC). Samples of technical powder (TP) were assayed to establish the LC50 and the potency of the product. The larvicidal activity of the TP and the tablet (T) were evaluated under SFC to assess the efficacy and the residual activity, measured against Ae. aegypti larvae. Either a T or 250 mg of TP were added to 50 L of water in plastic containers. Containers were exposed to sunlight or kept in the shade. Results showed a LC50 of 0.26 mg/L and a potency of 750 ITU/mg. In spite of differences in the toxicity amongst TP and T samples, all of them killed 98–100% of the larvae and the mortality remained high for six months, in the shade. The replacement of 20% or 60% of the water volume did not affect the activity of the product. Seasonal differences influenced the persistence of the product in containers exposed to sunlight. Both formulations showed an excellent performance, especially when kept in the shade. The Bti tablet evaluated in this study is potentially very useful in programs to control dengue vectors. 相似文献
10.
Can Sönmezer Rozemarijn Kleinendorst Dilek Imanci Guido Barzaghi Laura Villacorta Dirk Schübeler Vladimir Benes Nacho Molina Arnaud Regis Krebs 《Molecular cell》2021,81(2):255-267.e6
- Download : Download high-res image (261KB)
- Download : Download full-size image