全文获取类型
收费全文 | 184篇 |
免费 | 20篇 |
出版年
2021年 | 1篇 |
2019年 | 1篇 |
2017年 | 1篇 |
2015年 | 4篇 |
2014年 | 3篇 |
2013年 | 4篇 |
2012年 | 7篇 |
2011年 | 3篇 |
2010年 | 6篇 |
2009年 | 8篇 |
2008年 | 2篇 |
2007年 | 4篇 |
2006年 | 3篇 |
2005年 | 3篇 |
2004年 | 4篇 |
2003年 | 9篇 |
2002年 | 9篇 |
2001年 | 10篇 |
2000年 | 7篇 |
1999年 | 13篇 |
1998年 | 3篇 |
1997年 | 1篇 |
1996年 | 5篇 |
1995年 | 3篇 |
1994年 | 4篇 |
1993年 | 2篇 |
1992年 | 10篇 |
1991年 | 5篇 |
1990年 | 5篇 |
1989年 | 5篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1986年 | 5篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1981年 | 7篇 |
1980年 | 1篇 |
1979年 | 10篇 |
1978年 | 11篇 |
1977年 | 4篇 |
1975年 | 1篇 |
1974年 | 5篇 |
1973年 | 1篇 |
1969年 | 1篇 |
排序方式: 共有204条查询结果,搜索用时 15 毫秒
61.
Alternative heterocycles for DNA recognition: a 3-pyrazole/pyrrole pair specifies for G.C base pairs
Synthetic ligands comprising three aromatic amino acids, pyrrole (Py), imidazole (Im), and hydroxypyrrole (Hp), specifically recognize predetermined sequences as side-by-side pairs in the minor groove of DNA. To expand the repertoire of aromatic rings that may be utilized for minor groove recognition, three five-membered heterocyclic rings, 3-pyrazolecarboxylic acid (3-Pz), 4-pyrazolecarboxylic acid (4-Pz), and furan-2-carboxylic acid (Fr), were examined at the N-terminus of eight-ring hairpin polyamide ligands. The DNA binding properties of 3-Pz, 4-Pz, and Fr each paired with Py were studied by quantitative DNase I footprinting titrations on a 283 bp DNA restriction fragment containing four 6-bp binding sites 5'-ATNCCTAA-3' (N = G, C, A, or T; 6-bp polyamide binding site is underlined). The pair 3-Pz/Py has increased binding affinity and sequence specificity for G.C bp compared with Im/Py. 相似文献
62.
Gottesfeld JM Melander C Suto RK Raviol H Luger K Dervan PB 《Journal of molecular biology》2001,309(3):615-629
The ability of DNA-binding proteins to recognize their cognate sites in chromatin is restricted by the structure and dynamics of nucleosomal DNA, and by the translational and rotational positioning of the histone octamer. Here, we use six different pyrrole-imidazole polyamides as sequence-specific molecular probes for DNA accessibility in nucleosomes. We show that sites on nucleosomal DNA facing away from the histone octamer, or even partially facing the histone octamer, are fully accessible and that nucleosomes remain fully folded upon ligand binding. Polyamides only failed to bind where sites are completely blocked by interactions with the histone octamer. Removal of the amino-terminal tails of either histone H3 or histone H4 allowed these polyamides to bind. These results demonstrate that much of the DNA in the nucleosome is freely accessible for molecular recognition in the minor groove, and also support a role for the amino-terminal tails of H3 and H4 in modulating accessibility of nucleosomal DNA. 相似文献
63.
Targeted derepression of the human immunodeficiency virus type 1 long terminal repeat by pyrrole-imidazole polyamides 总被引:4,自引:0,他引:4 下载免费PDF全文
Coull JJ He G Melander C Rucker VC Dervan PB Margolis DM 《Journal of virology》2002,76(23):12349-12354
The host factor LSF represses the human immunodeficiency virus type 1 long terminal repeat (LTR) by mediating recruitment of histone deacetylase. We show that pyrrole-imidazole polyamides targeted to the LTR can specifically block LSF binding both in vitro and within cells via direct access to chromatin, resulting in increased LTR expression. 相似文献
64.
65.
66.
67.
David JJ Saliken Aillette Mulet-Sierra Nadr M Jomha Adetola B Adesida 《Arthritis research & therapy》2012,14(3):1-13
Introduction
The main objective of this study was to determine whether meniscus cells from the outer (MCO) and inner (MCI) regions of the meniscus interact similarly to or differently with mesenchymal stromal stem cells (MSCs). Previous study had shown that co-culture of meniscus cells with bone marrow-derived MSCs result in enhanced matrix formation relative to mono-cultures of meniscus cells and MSCs. However, the study did not examine if cells from the different regions of the meniscus interacted similarly to or differently with MSCs.Methods
Human menisci were harvested from four patients undergoing total knee replacements. Tissue from the outer and inner regions represented pieces taken from one third and two thirds of the radial distance of the meniscus, respectively. Meniscus cells were released from the menisci after collagenase treatment. Bone marrow MSCs were obtained from the iliac crest of two patients after plastic adherence and in vitro culture until passage 2. Primary meniscus cells from the outer (MCO) or inner (MCI) regions of the meniscus were co-cultured with MSCs in three-dimensional (3D) pellet cultures at 1:3 ratio, respectively, for 3 weeks in the presence of serum-free chondrogenic medium containing TGF-β1. Mono-cultures of MCO, MCI and MSCs served as experimental control groups. The tissue formed after 3 weeks was assessed biochemically, histochemically and by quantitative RT-PCR.Results
Co-culture of inner (MCI) or outer (MCO) meniscus cells with MSCs resulted in neo-tissue with increased (up to 2.2-fold) proteoglycan (GAG) matrix content relative to tissues formed from mono-cultures of MSCs, MCI and MCO. Co-cultures of MCI or MCO with MSCs produced the same amount of matrix in the tissue formed. However, the expression level of aggrecan was highest in mono-cultures of MSCs but similar in the other four groups. The DNA content of the tissues from co-cultured cells was not statistically different from tissues formed from mono-cultures of MSCs, MCI and MCO. The expression of collagen I (COL1A2) mRNA increased in co-cultured cells relative to mono-cultures of MCO and MCI but not compared to MSC mono-cultures. Collagen II (COL2A1) mRNA expression increased significantly in co-cultures of both MCO and MCI with MSCs compared to their own controls (mono-cultures of MCO and MCI respectively) but only the co-cultures of MCO:MSCs were significantly increased compared to MSC control mono-cultures. Increased collagen II protein expression was visible by collagen II immuno-histochemistry. The mRNA expression level of Sox9 was similar in all pellet cultures. The expression of collagen × (COL10A1) mRNA was 2-fold higher in co-cultures of MCI:MSCs relative to co-cultures of MCO:MSCs. Additionally, other hypertrophic genes, MMP-13 and Indian Hedgehog (IHh), were highly expressed by 4-fold and 18-fold, respectively, in co-cultures of MCI:MSCs relative to co-cultures of MCO:MSCs.Conclusions
Co-culture of primary MCI or MCO with MSCs resulted in enhanced matrix formation. MCI and MCO increased matrix formation similarly after co-culture with MSCs. However, MCO was more potent than MCI in suppressing hypertrophic differentiation of MSCs. These findings suggest that meniscus cells from the outer-vascular regions of the meniscus can be supplemented with MSCs in order to engineer functional grafts to reconstruct inner-avascular meniscus. 相似文献68.
69.
Karl Rumbold Hugo JJ van Buijsen Karin M Overkamp Johan W van Groenestijn Peter J Punt J van der Mariët Werf 《Microbial cell factories》2009,8(1):1-11
Although many secondary metabolites with diverse biological activities have been isolated from myxobacteria, most strains
of these biotechnologically important gliding prokaryotes remain difficult to handle genetically. In this study we describe
the new fast growing myxobacterial thermophilic isolate GT-2 as a heterologous host for the expression of natural product
biosynthetic pathways isolated from other myxobacteria. According to the results of sequence analysis of the 16S rDNA, this
moderately thermophilic isolate is closely related to Corallococcus macrosporus and was therefore named C. macrosporus GT-2. Fast growth of moderately thermophilic strains results in shorter fermentation and generation times, aspects which are of
significant interest for molecular biological work as well as production of secondary metabolites. Development of a genetic
manipulation system allowed the introduction of the complete myxochromide biosynthetic gene cluster, located on a transposable
fragment, into the chromosome of GT-2. Genetic engineering of the biosynthetic gene cluster by promoter exchange leads to
much higher production of myxochromides in the heterologous host C. macrosporus GT-2 in comparison to the original producer Stigmatella aurantiaca and to the previously described heterologous host Pseudomonas putida (600 mg/L versus 8 mg/L and 40 mg/L, respectively). 相似文献
70.
Annette AM Gerritsen Rob JPM Scholten Willem JJ Assendelft Herman Kuiper Henrica CW de Vet Lex M Bouter 《BMC neurology》2001,1(1):8-7