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排序方式: 共有145条查询结果,搜索用时 31 毫秒
71.
Bertho N Cerny J Kim YM Fiebiger E Ploegh H Boes M 《Journal of immunology (Baltimore, Md. : 1950)》2003,171(11):5689-5696
Activation of naive CD4 T cells by dendritic cells requires the sequential interaction of many TCR molecules with peptide-class II complexes of the appropriate specificity. Such interaction results in morphological transformation of class II MHC-containing endosomal compartments. In this study, we analyze the requirements for long tubular endosomal structures that polarize toward T cell contact sites using dendritic cells from I-A(b) class II -enhanced green fluorescent protein knock-in mice and I-A(b)-restricted CD4 T cells specific for OVA. Clustering of membrane proteins and ligation of T cell adhesion molecules LFA-1 and CD2 are involved in induction of endosomal tubulation. Activation of T cells increases their ability to induce class II-enhanced green fluorescent protein-positive tubules in dendritic cells, in part through up-regulation of CD40 ligand. Remarkably, and in stark contrast with the result obtained with dendritic cells loaded with intact OVA, OVA peptide added to dendritic cells failed to evoke T cell-polarized endosomal tubulation even though both conditions allowed T cell stimulation. These results suggest the existence of microdomains on the membrane of dendritic cells that allow Ag-specific T cells to evoke tubulation in the dendritic cell. 相似文献
72.
HLA-DR-mediated apoptosis susceptibility discriminates differentiation stages of dendritic/monocytic APC 总被引:3,自引:0,他引:3
Bertho N Drénou B Laupeze B Berre CL Amiot L Grosset JM Fardel O Charron D Mooney N Fauchet R 《Journal of immunology (Baltimore, Md. : 1950)》2000,164(5):2379-2385
Professional APC are characterized by their ability to present peptide via HLA class II in the presence of costimulatory molecules (CD40, CD80, and CD86). The efficiency of Ag presentation can be classed as follows: mature dendritic cells (DC) are most efficient, immature DC and macrophages are intermediate, and monocytes are considered poor APC. There is a large body of evidence demonstrating that HLA-DR transmits signals in the APC. In this study, we have addressed the question of the outcome of HLA-DR signals on APC of the monocyte/DC lineages throughout their differentiation from immature to mature APC. DC were generated from both monocytes and CD34+ cells of the same individual, macrophages were differentiated from monocytes. Immunophenotypical analysis clearly distinguished these populations. HLA-DR-mediated signals led to marked apoptosis in mature DC of either CD34 or monocytic origin. Significantly less apoptosis was observed in immature DC of either origin. Nonetheless, even immature DC were more susceptible to HLA-DR-mediated apoptosis than macrophages, whereas monocytes were resistant to HLA-DR-mediated apoptosis. The mechanism of HLA-DR-mediated apoptosis was independent of caspase activation. Taken together, these data lead to the notion that signals generated via HLA-DR lead to the demise of mature professional APC, thereby providing a means of limiting the immune response. 相似文献
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77.
Synhaeve N Stefani J Tourlonias E Dublineau I Bertho JM 《Radiation and environmental biophysics》2011,50(4):501-511
The aim of our study was to define the biokinetics of 90Sr after chronic contamination by ingestion using a juvenile and adult murine model. Animals ingested 90Sr by drinking water containing 20 kBq l−1 of 90Sr. For the juvenile model, parents received 90Sr before mating and their offspring were killed between birth and 20 weeks of ingestion. For the adult model, 90Sr ingestion started at 9 weeks of age and they were killed after different ingestion periods up to 20 weeks. The body weight,
food and water consumption of the animals were monitored on a weekly basis. Before killing and sampling of organs, animals
were put in metabolic cages. 90Sr in organs and excreta was determined by liquid scintillation β counting. Highest 90Sr contents were found in bones and were generally higher in females than in males, and 90Sr retention varied according to the skeletal sites. An accumulation of 90Sr in the bones was observed over time for both models, with a plateau level at adult age for the juvenile model. The highest
rate of 90Sr accumulation in bones was observed in early life of offspring, i.e. before the age of 6 weeks. With the exception of the
digestive tract, 90Sr was below the detection limit in all other organs sampled. Overall, our results confirm that 90Sr mainly accumulates in bones. Furthermore, our results indicate that there are gender- and age-dependent differences in
the distribution of 90Sr after low-dose chronic ingestion in the mouse model. These results provide the basis for future studies on possible non-cancerous
effects during chronic, long-term exposure to 90Sr through ingestion in a mouse model, especially on the immune and hematopoietic systems. 相似文献
78.
Transcutaneous delivery of vaccines to specific skin dendritic cells (DC) subsets is foreseen as a promising strategy to induce strong and specific types of immune responses such as tolerance, cytotoxicity or humoral immunity. Because of striking histological similarities between human and pig skin, pig is recognized as the most suitable model to study the cutaneous delivery of medicine. Therefore improving the knowledge on swine skin DC subsets would be highly valuable to the skin vaccine field. In this study, we showed that pig skin DC comprise the classical epidermal langerhans cells (LC) and dermal DC (DDC) that could be divided in 3 subsets according to their phenotypes: (1) the CD163(neg)/CD172a(neg), (2) the CD163(high)CD172a(pos) and (3) the CD163(low)CD172a(pos) DDC. These subtypes have the capacity to migrate from skin to lymph node since we detected them in pseudo-afferent lymph. Extensive phenotyping with a set of markers suggested that the CD163(high) DDC resemble the antibody response-inducing human skin DC/macrophages whereas the CD163(neg)CD172(low) DDC share properties with the CD8(+) T cell response-inducing murine skin CD103(pos) DC. This work, by showing similarities between human, mouse and swine skin DC, establishes pig as a model of choice for the development of transcutaneous immunisation strategies targeting DC. 相似文献
79.
Initial evaluation and follow-up of acute radiation syndrome in two patients from the Dakar accident
Jean Marc Bertho Laurence Roy Maâmar Souidi Marc Benderitter Eric Bey Radjini Racine 《Biomarkers》2013,18(2):94-102
The aim of this work was to evaluate and follow up the evolution of radiation damage in two victims of a radiation accident. Blood samples were used for cytogenetic evaluation of radiation dose and heterogeneity. The radiation dose estimates were 1 Gy and 2.3 Gy in the two most exposed patients. Plasma was used for the measurement of the Flt3 ligand as a marker of haematopoietic aplasia, citrulline for damage to the jejunal mucosal epithelium and oxysterols for damage to the liver, the central nervous system and the vascular compartment. The use of these biological indicators demonstrated the presence of a haematopoietic syndrome and suggested the presence of subclinical radiation-induced damage to the liver in one of the two patients. These results support the interest in using these biological indicators in order to evaluate radiation damage, especially in complex accidental situations. 相似文献
80.
The S4-S5 linker of KCNQ1 channels forms a structural scaffold with the S6 segment controlling gate closure 总被引:1,自引:0,他引:1
Labro AJ Boulet IR Choveau FS Mayeur E Bruyns T Loussouarn G Raes AL Snyders DJ 《The Journal of biological chemistry》2011,286(1):717-725
In vivo, KCNQ1 α-subunits associate with the β-subunit KCNE1 to generate the slowly activating cardiac potassium current (I(Ks)). Structurally, they share their topology with other Kv channels and consist out of six transmembrane helices (S1-S6) with the S1-S4 segments forming the voltage-sensing domain (VSD). The opening or closure of the intracellular channel gate, which localizes at the bottom of the S6 segment, is directly controlled by the movement of the VSD via an electromechanical coupling. In other Kv channels, this electromechanical coupling is realized by an interaction between the S4-S5 linker (S4S5(L)) and the C-terminal end of S6 (S6(T)). Previously we reported that substitutions for Leu(353) in S6(T) resulted in channels that failed to close completely. Closure could be incomplete because Leu(353) itself is the pore-occluding residue of the channel gate or because of a distorted electromechanical coupling. To resolve this and to address the role of S4S5(L) in KCNQ1 channel gating, we performed an alanine/tryptophan substitution scan of S4S5(L). The residues with a "high impact" on channel gating (when mutated) clustered on one side of the S4S5(L) α-helix. Hence, this side of S4S5(L) most likely contributes to the electromechanical coupling and finds its residue counterparts in S6(T). Accordingly, substitutions for Val(254) resulted in channels that were partially constitutively open and the ability to close completely was rescued by combination with substitutions for Leu(353) in S6(T). Double mutant cycle analysis supported this cross-talk indicating that both residues come in close contact and stabilize the closed state of the channel. 相似文献