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排序方式: 共有136条查询结果,搜索用时 46 毫秒
121.
122.
Nabbe KC van Lent PL Holthuysen AE Sloëtjes AW Koch AE Radstake TR van den Berg WB 《Arthritis research & therapy》2005,7(2):R392-R401
During immune-complex-mediated arthritis (ICA), severe cartilage destruction is mediated by Fcγ receptors (FcγRs) (mainly
FcγRI), cytokines (e.g. IL-1), and enzymes (matrix metalloproteinases (MMPs)). IL-13, a T helper 2 (Th2) cytokine abundantly
found in synovial fluid of patients with rheumatoid arthritis, has been shown to reduce joint inflammation and bone destruction
during experimental arthritis. However, the effect on severe cartilage destruction has not been studied in detail. We have
now investigated the role of IL-13 in chondrocyte death and MMP-mediated cartilage damage during ICA. IL-13 was locally overexpressed
in knee joints after injection of an adenovirus encoding IL-13 (AxCAhIL-13), 1 day before the onset of arthritis; injection
of AxCANI (an empty adenoviral construct) was used as a control. IL-13 significantly increased the amount of inflammatory
cells in the synovial lining and the joint cavity, by 30% to 60% at day 3 after the onset of ICA. Despite the enhanced inflammatory
response, chondrocyte death was diminished by two-thirds at days 3 and 7. The mRNA level of FcγRI, a receptor shown to be
crucial in the induction of chondrocyte death, was significantly down-regulated in synovium. Furthermore, MMP-mediated cartilage
damage, measured as neoepitope (VDIPEN) expression using immunolocalization, was halved. In contrast, mRNA levels of MMP-3,
-9, -12, and -13 were significantly higher and IL-1 protein, which induces production of latent MMPs, was increased fivefold
by IL-13. This study demonstrates that IL-13 overexpression during ICA diminished both chondrocyte death and MMP-mediated
VDIPEN expression, even though joint inflammation was enhanced. 相似文献
123.
Zaliauskiene L Kang S Sparks K Zinn KR Schwiebert LM Weaver CT Collawn JF 《Journal of immunology (Baltimore, Md. : 1950)》2002,169(5):2337-2345
Peptides, either as altered peptide ligands, competitors, or vaccines, offer an outstanding potential for regulating immune responses because of their exquisite specificity. However, a major problem associated with peptide therapies is that they are poorly taken up by APCs. Because of poor bioavailability, high concentrations and repeated treatments are required for peptide therapies in vivo. To circumvent this problem, we tested whether covalently coupling a peptide T cell determinant, OVA(323-339), to transferrin (Tf) enhances APC uptake and presentation as monitored by Th cell activation. Functional analysis of the Tf-peptide conjugates revealed that the conjugates were presented 10,000- and 100-fold more effectively by B cells than intact Ag and free peptide, respectively. Furthermore, we demonstrate that the Tf-peptide conjugates are taken up by B cells through a receptor-mediated process and subsequently delivered to the lysosomal compartment. Using an adoptive transfer assay, we show that that the Tf-peptide complexes are 100-fold more effective in vivo than the free peptide in activating CD4(+) T cells by following an early activation marker, CD69. Our results demonstrate that coupling peptides to Tf enhances peptide presentation, thereby making it possible to take full advantage of peptide-specific therapies in modulating T cell responses. 相似文献
124.
Extracellular ATP as a signaling molecule for epithelial cells 总被引:17,自引:0,他引:17
The charge of this invited review is to present a convincing case for the fact that cells release their ATP for physiological reasons. Many of our "purinergic" colleagues as well as ourselves have experienced resistance to this concept, because it is teleologically counter-intuitive. This review serves to integrate the three main tenets of extracellular ATP signaling: ATP release from cells, ATP receptors on cells, and ATP receptor-driven signaling within cells to affect cell or tissue physiology. First principles will be discussed in the Introduction concerning extracellular ATP signaling. All possible cellular mechanisms of ATP release will then be presented. Use of nucleotide and nucleoside scavengers as well as broad-specificity purinergic receptor antagonists will be presented as a method of detecting endogenous ATP release affecting a biological endpoint. Innovative methods of detecting released ATP by adapting luciferase detection reagents or by using "biosensors" will be presented.Because our laboratory has been primarily interested in epithelial cell physiology and pathophysiology for several years, the role of extracellular ATP in regulation of epithelial cell function will be the focus of this review. For ATP release to be physiologically relevant, receptors for ATP are required at the cell surface. The families of P2Y G protein-coupled receptors and ATP-gated P2X receptor channels will be introduced. Particular attention will be paid to P2X receptor channels that mediate the fast actions of extracellular ATP signaling, much like neurotransmitter-gated channels versus metabotropic heptahelical neurotransmitter receptors that couple to G proteins. Finally, fascinating biological paradigms in which extracellular ATP signaling has been implicated will be highlighted. It is the goal of this review to convert and attract new scientists into the exploding field of extracellular nucleotide signaling and to convince the reader that extracellular ATP is indeed a signaling molecule. 相似文献
125.
Schwiebert EM Liang L Cheng NL Williams CR Olteanu D Welty EA Zsembery A 《Purinergic signalling》2005,1(4):299-310
In this review, we focus on two attributes of P2X receptor channel function, one essential and one novel. First, we propose
that P2X receptors are extracellular sensors as well as receptors and ion channels. In particular, the large extracellular
domain (that comprises 70% of the molecular mass of the receptor channel protein) lends itself to be a cellular sensor. Moreover,
its exquisite sensitivity to extracellular pH, ionic strength, and multiple ligands evokes the function of a sensor. Second,
we propose that P2X receptors are extracellular zinc receptors as well as receptors for nucleotides. We provide novel data
in multiple publications and illustrative data in this invited review to suggest that zinc triggers ATP-independent activation
of P2X receptor channel function. In this light, P2X receptors are the cellular site of integration between autocrine and
paracrine zinc signaling and autocrine and paracrine purinergic signaling. P2X receptors may sense changes in these ligands
as well as in extracellular pH and ionic strength and transduce these sensations via calcium and/or sodium entry and changes
in membrane potential. 相似文献
126.
Djie Tjwan Thung Joep de Ligt Lisenka EM Vissers Marloes Steehouwer Mark Kroon Petra de Vries Eline P Slagboom Kai Ye Joris A Veltman Jayne Y Hehir-Kwa 《Genome biology》2014,15(10)
Mobile elements are major drivers in changing genomic architecture and can cause disease. The detection of mobile elements is hindered due to the low mappability of their highly repetitive sequences. We have developed an algorithm, called Mobster, to detect non-reference mobile element insertions in next generation sequencing data from both whole genome and whole exome studies. Mobster uses discordant read pairs and clipped reads in combination with consensus sequences of known active mobile elements. Mobster has a low false discovery rate and high recall rate for both L1 and Alu elements. Mobster is available at http://sourceforge.net/projects/mobster.
Electronic supplementary material
The online version of this article (doi:10.1186/s13059-014-0488-x) contains supplementary material, which is available to authorized users. 相似文献127.
128.
129.
K van Oers A W Santure I De Cauwer N EM van Bers R PMA Crooijmans B C Sheldon M E Visser J Slate M AM Groenen 《Heredity》2014,112(3):307-316
Linking variation in quantitative traits to variation in the genome is an important, but
challenging task in the study of life-history evolution. Linkage maps provide a valuable
tool for the unravelling of such trait−gene associations. Moreover, they give
insight into recombination landscapes and between-species karyotype evolution. Here we
used genotype data, generated from a 10k single-nucleotide polymorphism (SNP) chip, of
over 2000 individuals to produce high-density linkage maps of the great tit (Parus
major), a passerine bird that serves as a model species for ecological and
evolutionary questions. We created independent maps from two distinct populations: a
captive F2-cross from The Netherlands (NL) and a wild population from the United Kingdom
(UK). The two maps contained 6554 SNPs in 32 linkage groups, spanning 2010 cM and
1917 cM for the NL and UK populations, respectively, and were similar in size and
marker order. Subtle levels of heterochiasmy within and between chromosomes were
remarkably consistent between the populations, suggesting that the local departures from
sex-equal recombination rates have evolved. This key and surprising result would have been
impossible to detect if only one population was mapped. A comparison with zebra finch
Taeniopygia guttata, chicken Gallus gallus and the green anole lizard
Anolis carolinensis genomes provided further insight into the evolution of
avian karyotypes. 相似文献
130.