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排序方式: 共有153条查询结果,搜索用时 15 毫秒
51.
The CCL2 CCR2 axis is likely to contributes to the development and progression of cancer diseases by two major mechanisms; autocrine effect of CCL2 as a survival/growth factor for CCR2+ cancer cells and, the attraction of CCR2+ CX3CR1+tumor associated macrophages that in the absence of CCR2 hardly migrate. Thus far no in vivo system has been set up to differentiate the selective contribution of each of these features to cancer development. Here we employed a chimera animal model in which all non-malignant cells are CCR2−/−, but all cancer cells are CCR2+, combined with an adoptive transfer system of bone marrow (BM) CX3CR1+ cells from CCR2+ mice harboring a targeted replacement of the CX3CR1gene by an enhanced green fluorescent protein (EGFP) reporter gene (cx3cr1
gfp), together with the CD45.1 congene. Using this system we dissected the selective contribution of CX3CR1+CCR2+ cells, which comprise only about 7% of CD11b+ BM cells, to tumor development and angiogenesis. Showing that aside for their direct pro-angiogenic effect they are essential for the recruitment of other CD11b+ cells to the tumor site. We further show that the administration of CCR2-Ig, that selectively and specifically neutralize CCL2, to mice in which CCR2 is expressed only on tumor cells, further suppressed tumor development, implicating for the key role of this chemokine supporting tumor survival in an autocrine manner. This further emphasizes the important role of CCL2 as a target for therapy of cancer diseases. 相似文献
52.
An important and common problem in microarray experiments is the detection of genes that are differentially expressed in a given number of classes. As this problem concerns the selection of significant genes from a large pool of candidate genes, it needs to be carried out within the framework of multiple hypothesis testing. In this paper, we focus on the use of mixture models to handle the multiplicity issue. With this approach, a measure of the local FDR (false discovery rate) is provided for each gene. An attractive feature of the mixture model approach is that it provides a framework for the estimation of the prior probability that a gene is not differentially expressed, and this probability can subsequently be used in forming a decision rule. The rule can also be formed to take the false negative rate into account. We apply this approach to a well-known publicly available data set on breast cancer, and discuss our findings with reference to other approaches. 相似文献
53.
Liat Shavit Grievink David Penny Mike D Hendy Barbara R Holland 《BMC evolutionary biology》2008,8(1):317
Background
Commonly used phylogenetic models assume a homogeneous evolutionary process throughout the tree. It is known that these homogeneous models are often too simplistic, and that with time some properties of the evolutionary process can change (due to selection or drift). In particular, as constraints on sequences evolve, the proportion of variable sites can vary between lineages. This affects the ability of phylogenetic methods to correctly estimate phylogenetic trees, especially for long timescales. To date there is no phylogenetic model that allows for change in the proportion of variable sites, and the degree to which this affects phylogenetic reconstruction is unknown. 相似文献54.
Hallak M Vazana L Shpilberg O Levy I Mazar J Nathan I 《Apoptosis : an international journal on programmed cell death》2008,13(1):147-155
Mimosine, a non-protein amino acid, is mainly known for its action as a reversible inhibitor of DNA replication and, therefore,
has been widely used as a cell cycle synchronizing agent. Recently, it has been shown that mimosine also induces apoptosis,
as mainly reflected in its ability to elicit characteristic nuclear changes. The present study elucidates the mechanism underlying
mimosine’s apoptotic effects, using the U-937 leukemia cell line. We now demonstrate that in isolated rat liver mitochondria,
mimosine induces mitochondrial swelling that can be inhibited by cyclosporine A, indicative of permeability transition (PT)
mega-channel opening. Mimosine-induced apoptosis was accompanied by formation of hydrogen peroxide and a decrease in reduced
glutathione levels. The apoptotic process was partially inhibited by cyclosporine A and substantially blocked by the antioxidant
N-acetylcysteine, suggesting an essential role for reactive oxygen species formation during the apoptotic processes. The apoptosis
induced by mimosine was also accompanied by a decrease in mitochondrial membrane potential, cytochrome c release and caspase 3 and 9 activation. Our results thus imply that mimosine activates apoptosis through mitochondrial activation
and formation of H2O2, both of which play functional roles in the induction of cell death.
Maher Hallak and Liat Vazana have contributed equally to the work. 相似文献
55.
A computerized tank system for studying the effect of temperature on calcification of reef organisms
Liat Abramovitch-Gottlib David Katoshevski Razi Vago 《Journal of biochemical and biophysical methods》2002,50(2-3):245-252
Mediated by algal symbionts, calcification in reef building corals is one of the important processes, which enable coral's growth. In the present study, we used a buoyant weighing technique to study calcification of two coralline species, Stylophora pistillata and the hydrocoral Millepora dichotoma. The colonies were grown in a tank system, in which light, nutrition and water motion were kept constant and temperature was elevated by means of a computerized controlled apparatus. An almost constant rate of calcification was observed in the two species at 22-28 degrees C. Elevation of the temperature above this range to 29-31 degrees C caused a slow down in calcification in both species. A grater number of S. pistillata colonies became bleached at temperatures of >or=29 degrees C, whereas M. dichotoma colonies suffered from bleaching only after three days at 31 degrees C. For both species, control groups, remained viable during the experimental period. The differences in responses to changes in temperature of the two species may be as a consequence of different adaptive mechanisms or to different susceptibilities of the corals to elevated temperatures. We have shown that elevating temperatures above annual maximal ranges have a significant effect on coral calcification. We also demonstrated that sessile calcified marine organisms having ecological and biomedical significance could be cultured and manipulated under laboratory conditions. 相似文献
56.
57.
Guntram Borck Liat de Vries Hsin-Jung Wu Pola Smirin-Yosef Gudrun Nürnberg Irina Lagovsky Luis Henrique Ishida Patrick Thierry Dagmar Wieczorek Peter Nürnberg John Foley Christian Kubisch Lina Basel-Vanagaite 《Human genetics》2014,133(8):1041-1047
Athelia is a very rare entity that is defined by the absence of the nipple–areola complex. It can affect either sex and is mostly part of syndromes including other congenital or ectodermal anomalies, such as limb-mammary syndrome, scalp–ear–nipple syndrome, or ectodermal dysplasias. Here, we report on three children from two branches of an extended consanguineous Israeli Arab family, a girl and two boys, who presented with a spectrum of nipple anomalies ranging from unilateral hypothelia to bilateral athelia but no other consistently associated anomalies except a characteristic eyebrow shape. Using homozygosity mapping after single nucleotide polymorphism (SNP) array genotyping and candidate gene sequencing we identified a homozygous frameshift mutation in PTPRF as the likely cause of nipple anomalies in this family. PTPRF encodes a receptor-type protein phosphatase that localizes to adherens junctions and may be involved in the regulation of epithelial cell–cell contacts, peptide growth factor signaling, and the canonical Wnt pathway. Together with previous reports on female mutant Ptprf mice, which have a lactation defect, and disruption of one allele of PTPRF by a balanced translocation in a woman with amastia, our results indicate a key role for PTPRF in the development of the nipple–areola region. 相似文献
58.
Levin-Salomon V Maayan I Avrahami-Moyal L Marbach I Livnah O Engelberg D 《The Biochemical journal》2009,417(1):331-340
MAPKs (mitogen-activated protein kinases) are key components in cell signalling pathways. Under optimal growth conditions, their activity is kept off, but in response to stimulation it is dramatically evoked. Because of the high degree of evolutionary conservation at the levels of sequence and mode of activation, MAPKs are believed to share similar regulatory mechanisms in all eukaryotes and to be functionally substitutable between them. To assess the reliability of this notion, we systematically analysed the activity, regulation and phenotypic effects of mammalian MAPKs in yeast. Unexpectedly, all mammalian MAPKs tested were spontaneously phosphorylated in yeast. JNKs (c-Jun N-terminal kinases) lost their phosphorylation in pbs2Delta cells, but p38s and ERKs (extracellular-signal-regulated kinases) maintained their spontaneous phosphorylation even in pbs2Deltaste7Deltamkk1Deltamkk2Delta cells. Kinase-dead variants of ERKs and p38s were phosphorylated in strains lacking a single MEK (MAPK/ERK kinase), but not in pbs2Deltaste7Deltamkk1Deltamkk2Delta cells. Thus, in yeast, p38 and ERKs are phosphorylated via a combined mechanism of autophosphorylation and MEK-mediated phosphorylation (any MEK). We further addressed the mechanism allowing mammalian MAPKs to exploit yeast MEKs in the absence of any activating signal. We suggest that mammalian MAPKs lost during evolution a C-terminal region that exists in some yeast MAPKs. Indeed, removal of this region from Hog1 and Mpk1 rendered them spontaneously and highly phosphorylated. It implies that MAPKs possess an efficient inherent autoposphorylation capability that is suppressed in yeast MAPKs via a C-terminal domain and in mammalian MAPKs via as yet unknown means. 相似文献
59.
Einat Zalckvar Hanna Berissi Liat Mizrachy Yulia Idelchuk Itay Koren Miriam Eisenstein Helena Sabanay Ronit Pinkas‐Kramarski Adi Kimchi 《EMBO reports》2009,10(3):285-292
Autophagy, an evolutionarily conserved process, has functions both in cytoprotective and programmed cell death mechanisms. Beclin 1, an essential autophagic protein, was recently identified as a BH3‐domain‐only protein that binds to Bcl‐2 anti‐apoptotic family members. The dissociation of beclin 1 from its Bcl‐2 inhibitors is essential for its autophagic activity, and therefore should be tightly controlled. Here, we show that death‐associated protein kinase (DAPK) regulates this process. The activated form of DAPK triggers autophagy in a beclin‐1‐dependent manner. DAPK phosphorylates beclin 1 on Thr 119 located at a crucial position within its BH3 domain, and thus promotes the dissociation of beclin 1 from Bcl‐XL and the induction of autophagy. These results reveal a substrate for DAPK that acts as one of the core proteins of the autophagic machinery, and they provide a new phosphorylation‐based mechanism that reduces the interaction of beclin 1 with its inhibitors to activate the autophagic machinery. 相似文献
60.
Liat Haklai‐Topper Guy Mlechkovich Dana Savariego Irena Gokhman Avraham Yaron 《The EMBO journal》2010,29(15):2635-2645
The correct navigation of axons to their targets depends on guidance molecules in the extra‐cellular environment. Differential responsiveness to a particular guidance cue is largely an outcome of disparity in the expression of its receptors on the reacting axons. Here, we show that the differential responsiveness of sympathetic and sensory neurons to the transmembrane Semaphorin Sema6A is mainly determined by its co‐expression in the responding neurons. Both sympathetic and sensory neurons express the Sema6A receptor Plexin‐A4, but only sympathetic neurons respond to it. The expression of Sema6A counteracts this responsiveness and is detected only in sensory neurons. Remarkably, sensory neurons that lack Sema6A gain sensitivity to it in a Plexin‐A4‐dependent manner. Using heterologus systems, we show that the co‐expression of Sema6A and Plexin‐A4 hinders the binding of exogenous ligand, suggesting that a Sema6A–Plexin‐A4 cis interaction serves as an inhibitory mechanism. Finally, we provide evidence for differential modes of interaction in cis versus in trans. Thus, co‐expression of a transmembrane cue together with its receptor can serve as a guidance response modulator. 相似文献