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1.
Target Detection Assay (TDA): a versatile procedure to determine DNA binding sites as demonstrated on SP1 protein. 总被引:34,自引:10,他引:24 下载免费PDF全文
We developed a rapid method designated Target Detection Assay (TDA) to determine DNA binding sites for putative DNA binding proteins. A purified, functionally active DNA binding protein and a pool of random double-stranded oligonucleotides harbouring PCR primer sites at each end are included the TDA cycle which consists of four separate steps: a DNA protein incubation step, a protein DNA complex separation step, a DNA elution step and a polymerase chain reaction (PCR) DNA amplification step. The stringency of selection can be increased in consecutive TDA cycles. Since tiny amounts of retained DNA can be rescued by PCR, buffer systems, salt concentrations and competitor DNA contents can be varied in order to determine high affinity binding sites for the protein of choice. To test the efficiency of the TDA procedure potential DNA binding sites were selected by the DNA binding protein SP1 from a pool of oligonucleotides with random nucleotides at 12 positions. Target sites selected by recombinant SP1 closely matched the SP1 consensus site. If DNA recognition sites have to be determined for known, mutated or putative DNA binding proteins, the Target Detection Assay (TDA) is a versatile and rapid technique for consideration. 相似文献
2.
Summary Two members of the human zinc finger Krüppel family, ZNF 12 (KOX 3) and ZNF 26 (KOX 20), have been localized by somatic cell hybrid analysis and in situ chromosomal hybridization. The presence of individual human zinc finger genes in mouse-human hybrid DNAs was correlated with the presence of specific human chromosomes or regions of chromosomes in the corresponding cell hybrids. Analysis of such mouse-human hybrid DNAs allowed the assignment of the ZNF 12 (KOX 3) gene to chromosome region 7p. The ZNF 26 (KOX 20) gene segregated with chromosome region 12q13-qter. The zinc finger genes ZNF 12 (KOX 3) and ZNF 26 (KOX 20) were localized by in situ chromosomal hybridization to human chromosome regions 7p22-21 and 12q24.33, respectively. These genes and the previously mapped ZNF 24 (KOX 17) and ZNF 29 (KOX 26) genes, are found near fragile sites. 相似文献
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Chromosomal localization of two human zinc finger protein genes, ZNF24 (KOX17) and ZNF29 (KOX26), to 18q12 and 17p13-p12, respectively 总被引:1,自引:0,他引:1
Two members of the zinc finger Krüppel family, ZNF24 (KOX17) and ZNF29 (KOX26), have been localized by somatic cell hybrid analysis and in situ chromosomal hybridization to human chromosomes 18q12 and 17p13-p12, respectively. The mapping of ZNF29 together with the previously reported localization of ZFP3 suggests that a zinc finger gene complex is located on human chromosome 17p. ZNF29 maps centromeric to the human p53 tumor antigen gene (TP53). In the analogous murine position, the two mouse zinc finger genes Zfp2 and Zfp3 have recently been assigned to the distal region of mouse chromosome 11, the murine homolog of human chromosome 17. Both human zinc finger genes ZNF24 and ZNF29 are in chromosomal regions that have been noted to be deleted in neoplasms of the lung and of the central nervous system at chromosome 17p and in colorectal neoplasia at chromosomes 17p and 18q. 相似文献
5.
Joan Thiesen Torben S. Christensen Thomas G. Kristensen Rikke D. Andersen Brit Brunoe Trine K. Gregersen Mikkel Thrane Bo P. Weidema 《The International Journal of Life Cycle Assessment》2008,13(2):104-114
Goal, Scope and Background Traditionally, comparative life cycle assessments (LCA) have not considered rebound effects, for instance in case of significant
price differences among the compared products. No justifications have been made for this delimitation in scope. This article
shows that price differences and the consequent effects of marginal consumer expenditure may influence the conclusions of
comparative LCA significantly. We also show that considerations about rebound effects of price differences can be included
in LCAs.
Methods The direct rebound effect of a price difference is marginal consumption. Based on statistical data on private consumption
in different income groups (Statistics Denmark 2005a, 2005b), the present article provides an estimate of how an average Danish
household will spend an additional 1 DKK for further consumer goods, when the household has gained money from choosing a cheaper
product alternative. The approach is to use marginal income changes and the following changes in consumption patterns as an
expression for marginal consumption. Secondly, the environmental impact potentials related to this marginal consumption are
estimated by the use of environmental impact intensity data from an IO-LCA database (Weidema et al. 2005). Finally, it is
discussed whether, and in which ways the conclusions of comparative LCAs can be affected by including the price difference
between product alternatives. This is elucidated in a case study of a comparative LCA screening of two different kinds of
Danish cheese products (Fricke et al. 2004).
Results Car purchase and driving, use and maintenance of dwelling, clothing purchase and insurance constitutes the largest percentages
of the marginal consumption. In a case study of two cheeses, the including the impact potentials related to the price difference
results in significant changes in the total impact potentials. Considering the relatively small price difference of the two
products, it is likely also to have a significant influence on the results of comparative LCAs more generally.
Discussion The influence of marginal consumption in comparative LCAs is relevant to consider in situations with large differences in
the price of the product alternatives being compared, and in situations with minor differences in the impact potentials related
to the alternatives. However, different uncertainties are linked to determining the pattern for marginal consumption and the
environmental impact potential related to this. These are first of all related to the method used, but also include inaccurate
data of consumption in households, aggregation and weighting of income groups, aggregation of product groups, estimation and
size of the price difference, and the general applicability of the results.
Conclusion Incorporating marginal consumption in consequential LCAs is possible in practice. In the case study used, including the rebound
effects of the price difference has a significant influence on the result of the comparative LCA, as the result for the impact
categories acidification and nutrient enrichment changes in favour of the expensive product.
Recommendations and Perspectives It is recommended that the rebound effects of price differences should be included more frequently in LCAs. In order to ensure
this, further research in marginal consumption and investment patterns and IO data for different countries or regions is required.
Furthermore, this study does not consider the economic distributional consequences of buying an expensive product instead
of a cheaper product (e.g. related to how the profit is spent by those who provided the product). It should also be noted,
that more expensive products not necessarily result in less consumption, as those who provided the product also will spend
the money they have earned from the sale. Ideally, these consequences should also be further investigated. Likewise, the development
of databases to include marginal consumption in PC-tools is needed. In general, considerations of marginal consumption would
favour expensive product alternatives, depending, however, on the type of consumer.
ESS-Submission Editor: Dr. David Hunkeler (david.hunkeler@aquaplustech.ch) 相似文献
6.
Mitja Lu?trek Peter Lorenz Michael Kreutzer Zilliang Qian Felix Steinbeck Di Wu Nadine Born Bjoern Ziems Michael Hecker Miri Blank Yehuda Shoenfeld Zhiwei Cao Michael O. Glocker Yixue Li Georg Fuellen Hans-Jürgen Thiesen 《PloS one》2013,8(11)
Epitope-antibody-reactivities (EAR) of intravenous immunoglobulins (IVIGs) determined for 75,534 peptides by microarray analysis demonstrate that roughly 9% of peptides derived from 870 different human protein sequences react with antibodies present in IVIG. Computational prediction of linear B cell epitopes was conducted using machine learning with an ensemble of classifiers in combination with position weight matrix (PWM) analysis. Machine learning slightly outperformed PWM with area under the curve (AUC) of 0.884 vs. 0.849. Two different types of epitope-antibody recognition-modes (Type I EAR and Type II EAR) were found. Peptides of Type I EAR are high in tyrosine, tryptophan and phenylalanine, and low in asparagine, glutamine and glutamic acid residues, whereas for peptides of Type II EAR it is the other way around. Representative crystal structures present in the Protein Data Bank (PDB) of Type I EAR are PDB 1TZI and PDB 2DD8, while PDB 2FD6 and 2J4W are typical for Type II EAR. Type I EAR peptides share predicted propensities for being presented by MHC class I and class II complexes. The latter interaction possibly favors T cell-dependent antibody responses including IgG class switching. Peptides of Type II EAR are predicted not to be preferentially presented by MHC complexes, thus implying the involvement of T cell-independent IgG class switch mechanisms. The high extent of IgG immunoglobulin reactivity with human peptides implies that circulating IgG molecules are prone to bind to human protein/peptide structures under non-pathological, non-inflammatory conditions. A webserver for predicting EAR of peptide sequences is available at www.sysmed-immun.eu/EAR. 相似文献
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Pahnke J Mix E Knoblich R Müller J Zschiesche M Schubert B Koczan D Bauer P Böttcher T Thiesen HJ Lazarov L Wree A Rolfs A 《Experimental cell research》2004,297(2):484-494
The glial cell line-derived neurotrophic factor (GDNF) is involved in the development and maintenance of neural tissues. Mutations in components of its signaling pathway lead to severe migration deficits of neuronal crest stem cells, tumor formation, or ablation of the urinary system. In animal models of Parkinson's disease, GDNF has been recognized to be neuroprotective and to improve motor function when delivered into the cerebral ventricles or into the substantia nigra. Here, we characterize the network of 43 genes induced by GDNF overproduction of neuronal progenitor cells (ST14A), which mainly regulate migration and differentiation of neuronal progenitor cells. GDNF down-regulates doublecortin, Paf-ah1b (Lis1), dynamin, and alpha-tubulin, which are involved in neocortical lamination and cytoskeletal reorganization. Axonal guidance depends on cell-surface molecules and extracellular matrix proteins. Laminin, Mpl3, Alcam, Bin1, Id1, Id2, Id3, neuregulin1, the ephrinB2-receptor, neuritin, focal adhesion kinase (FAK), Tc10, Pdpk1, clusterin, GTP-cyclooxygenase1, and follistatin are genes up-regulated by GDNF overexpression. Moreover, we found four key enzymes of the cholesterol-synthesis pathway to be down-regulated leading to decreased farnesyl-pyrophospate production. Many proteins are anchored by farnesyl-derivates at the cell membrane. The identification of these GDNF-regulated genes may open new opportunities for directly influencing differentiation and developmental processes of neurons. 相似文献
10.
Dirk Pohlers Andreas Beyer Dirk Koczan Thomas Wilhelm Hans-Jürgen Thiesen Raimund W Kinne 《Arthritis research & therapy》2007,9(3):R59
Genome-wide gene expression was comparatively investigated in early-passage rheumatoid arthritis (RA) and osteoarthritis (OA)
synovial fibroblasts (SFBs; n = 6 each) using oligonucleotide microarrays; mRNA/protein data were validated by quantitative PCR (qPCR) and western blotting
and immunohistochemistry, respectively. Gene set enrichment analysis (GSEA) of the microarray data suggested constitutive
upregulation of components of the transforming growth factor (TGF)-β pathway in RA SFBs, with 2 hits in the top 30 regulated
pathways. The growth factor TGF-β1, its receptor TGFBR1, the TGF-β binding proteins LTBP1/2, the TGF-β-releasing thrombospondin
1 (THBS1), the negative effector SkiL, and the smad-associated molecule SARA were upregulated in RA SFBs compared to OA SFBs,
whereas TGF-β2 was downregulated. Upregulation of TGF-β1 and THBS1 mRNA (both positively correlated with clinical markers
of disease activity/severity) and downregulation of TGF-β2 mRNA in RA SFBs were confirmed by qPCR. TGFBR1 mRNA (only numerically
upregulated in RA SFBs) and SkiL mRNA were not differentially expressed. At the protein level, TGF-β1 showed a slightly higher
expression, and the signal-transducing TGFBR1 and the TGF-β-activating THBS1 a significantly higher expression in RA SFBs
than in OA SFBs. Consistent with the upregulated TGF-β pathway in RA SFBs, stimulation with TGF-β1 resulted in a significantly
enhanced expression of matrix-metalloproteinase (MMP)-11 mRNA and protein in RA SFBs, but not in OA SFBs. In conclusion, RA
SFBs show broad, constitutive alterations of the TGF-β pathway. The abundance of TGF-β, in conjunction with an augmented mRNA
and/or protein expression of TGF-β-releasing THBS1 and TGFBR1, suggests a pathogenetic role of TGF-β-induced effects on SFBs
in RA, for example, the augmentation of MMP-mediated matrix degradation/remodeling. 相似文献