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141.
142.
Wenzel TJ Miles RD Zomlefer K Frederique DE Roan MA Troughton JS Pond BV Colby AL 《Chirality》2000,12(1):30-37
A metal chelating ligand is bonded to alpha-, beta-, and gamma-cyclodextrin by the reaction of diethylenetraminepentaacetic dianhydride with the corresponding 6-mono- and 2-mono(amine)cyclodextrin. Adding Dy(III) to the cyclodextrin derivatives causes shifts in the (1)H-NMR spectra of substrates such as propranolol, tryptophan, aspartame, carbinoxamine, pheniramine, doxylamine, and 1-anilino-8-naphthalenesulfonate. The Dy(III)-induced shifts enhance the enantiomeric resolution in the NMR spectra of several substrates. Enhancements in enantiomeric resolution using cyclodextrin derivatives with the amine tether are compared to previously described compounds in which the chelating ligand is attached through an ethylenediamine tether. In general, the Dy(III) complex of the 6-beta-derivative with the amine tether is a more effective chiral resolving agent than the complex with the ethylenediamine tether. The opposite trend is observed with the 2-beta-derivatives. The presence of the chelating ligand in the 2-beta-derivative hinders certain substrates from entering the cavity. For cationic substrates, evidence suggests that a cooperative association involving inclusion in the cavity and association with the Dy(III) unit occurs. Enhancements in enantiomeric resolution in the spectrum of tryptophan are greater for the secondary alpha- and gamma-derivatives than the beta-derivative. 相似文献
143.
A genome‐wide association study in Caucasian women suggests the involvement of HLA genes in the severity of facial solar lentigines 下载免费PDF全文
Khaled Ezzedine Randa Jdid Lieng Taing Taoufik Labib Cedric Coulonges Damien Ulveling Wassila Carpentier Pilar Galan Serge Hercberg Frederique Morizot Julie Latreille Denis Malvy Erwin Tschachler Jean‐François Zagury 《Pigment cell & melanoma research》2016,29(5):550-558
Solar lentigines are a common feature of sun‐induced skin ageing. Little is known, however, about the genetic factors contributing to their development. In this genome‐wide association study, we aimed to identify genetic loci associated with solar lentigines on the face in 502 middle‐aged French women. Nine SNPs, gathered in two independent blocks on chromosome 6, exhibited a false discovery rate below 25% when looking for associations with the facial lentigine score. The first block, in the 6p22 region, corresponded to intergenic SNPs and also exhibited a significant association with forehead lentigines (P = 1.37 × 10?8). The second block, within the 6p21 HLA region, was associated with decreased HLA‐C expression according to several eQTL databases. Interestingly, these SNPs were also in high linkage disequilibrium with the HLA‐C*0701 allele (r2 = 0.95). We replicated an association recently found by GWAS in the IRF4 gene. Finally, a complementary study on 44 selected candidate SNPs revealed novel associations in the MITF gene. Overall, our results point to several mechanisms involved in the severity of facial lentigines, including HLA/immunity and the melanogenesis pathway. 相似文献
144.
Frederique M Moret Kim MG van der Wurff-Jacobs Johannes WJ Bijlsma Floris PJG Lafeber Joel AG van Roon 《Arthritis research & therapy》2014,16(6)
Introduction
The aim of this study was to investigate PD-1/PD-L1 involvement in the hyporesponsiveness of rheumatoid arthritis (RA) synovial fluid (SF) CD4 T cells upon stimulation by thymic stromal lymphopoietin (TSLP)–primed CD1c myeloid dendritic cells (mDCs).Methods
Expression of PD-1 on naïve (Tn), central memory (Tcm) and effector memory (Tem) CD4 T cell subsets was assessed by flow cytometry. PD-L1 expression and its regulation upon TSLP stimulation of mDCs from peripheral blood (PB) and SF of RA patients were investigated by quantitative RT-PCR and flow cytometry. The involvement of PD-1/PD-L1 interactions in SF T cell hyporesponsiveness upon (TSLP-primed) mDC activation was determined by cell culture in the presence of PD-1 blocking antibodies, with or without interleukin 7 (IL-7) as a recognized suppressor of PD-1 expression.Results
PD-1 expression was increased on CD4 T cells derived from SF compared with PB of RA patients. TSLP increased PD-L1 mRNA expression in both PB and SF mDCs. PD-L1 protein expression was increased on SF mDCs compared with PB mDCs and was associated with T cell hyporesponsiveness. Blockade of PD-1, as well as IL-7 stimulation, during cocultures of memory T cells and (TSLP-primed) mDCs from RA patients significantly recovered T cell proliferation.Conclusion
SF T cell hyporesponsiveness upon (TSLP-primed) mDC stimulation in RA joints is partially dependent on PD-1/PD-L1 interactions, as PD-1 and PD-L1 are both highly expressed on SF T cells and mDCs, respectively, and inhibiting PD-1 availability restores T cell proliferation. The potential of IL-7 to robustly reverse this hyporesponsiveness suggests that such proinflammatory cytokines in RA joints strongly contribute to memory T cell activation. 相似文献145.
N'Guyen QB Fallone F Seree E Fina F Villard PH Guigal N De Meo M Lacarelle B Martin PM Barra Y 《Biochemical and biophysical research communications》2002,295(2):249-254
Mice with a targeted null mutation of the serotonin 5-HT(2C) receptor gene exhibit hyperphagia that leads to a late-onset obesity. Here we show that oxygen consumption was decreased in fed and fasted obese mutants. No phenotypic differences were observed in uncoupling protein-1 (UCP-1) mRNA levels in brown adipose tissues and UCP-3 mRNA in skeletal muscle. UCP-2 mRNA levels were significantly increased in white adipose tissue (4-fold) and skeletal muscle (47%) in older obese mutant mice, whereas UCP-2 mRNA in liver are significantly increased in both young lean (54% increase) and older obese (52% increase) mutant mice. In contrast, 5-HT(2C) receptor mutants displayed age-dependent decreases in beta 3-adrenergic receptor (beta 3-AR) mRNA levels in white adipose tissue, however, no such changes were observed in brown adipose tissue. These results indicate that a mutation of 5-HT(2C) receptor gene leads to a secondary decrease in beta 3-AR gene expression that is related to enhanced adiposity. 相似文献
146.
Frederique Valentin Francesco d'Errico 《American journal of physical anthropology》1995,98(3):375-390
Human remains giving direct evidence concerning the history of dissection practices are rare. Thirteen cranial fragments which bear evidence of having been purposely cut and sawn were discovered in a crypt during excavations undertaken in Sens (Yonne, France). Ceramics date these remains to the period from the end of the XIVth to the end of the XVIth centuries. Nine individuals are represented: one adolescent and eight adults of both sexes. The position of the cutmarks, which' were produced by a long, sharp cutting tool, show that the scalp was completely removed from the skull. The sawing, which was done with a large-toothed saw, was both clockwise and counterclockwise in direction. The sawn surfaces reveal a deliberate attempt not to damage the brain. This procedure is compared to that of modern autopsies. The remains from Sens are also compared with several other sawn cranial fragments recently discovered in France and England. Three hypotheses are discussed: embalmment, autopsy, and anatomical studies. Analysis of these remains and historical documentation suggest embalmment and/or autopsy as the probable purpose of the opening of the skull. © 1995 Wiley-Liss, Inc. 相似文献
147.
Jonas Tjaden Lukas Pieczora Frederique Wach Carsten Theiss Verena Theis 《Cellular and molecular neurobiology》2018,38(7):1399-1412
Primary neurons are difficult to cultivate because they are often part of a complex tissue, and synaptically connected to numerous other cell types. These circumstances often prevent us from unveiling molecular and metabolic mechanisms of distinct cells, as functional signals or assays cannot clearly be correlated with them due to interfering signals from other parts of the culture. We therefore present an up-to-date method for obtaining a highly purified neuronal culture of Purkinje cells. In the past, Purkinje cells were successfully isolated from young mouse cerebella, but this protocol was never adapted to other mammals. We therefore provide an updated and adjusted protocol for Purkinje cell isolation from rat instead of mouse cerebella. To purify Purkinje cells, we obtained perinatal rat cerebella, dissociated them and performed a Percoll gradient centrifugation to segregate the smaller and larger cell fractions. In a second step, we performed an immunopanning procedure to enrich only Purkinje cells from the large cell fraction. Based on former protocols, we used a different antibody for the immunopanning procedure and adjusted several aspects from the initial protocol to improve the yield and vitality of Purkinje cells. We provide RT-qPCR-based purity data obtained with this protocol and show the behaviour and the growth of these purified Purkinje cells. We provide a highly reproducible purification protocol for Purkinje cell cultures of high purity that allows functional analysis and downstream assays on living rat Purkinje cells and further morphological growth analysis in future. 相似文献
148.
Reproductive physiology depends on the control of biosynthesis in the pituitary gonadotrope by hypothalamic gonadotropin-releasing hormone (GnRH). The responses to GnRH include activation of extracellular signal-regulated kinase (ERK) and induction of Egr1. Using population and single cell signaling assays, we investigated the signal and noise transmission through this signaling and gene circuit, analyzing data obtained from 43,775 individual cells in 40 experiments. After exposure to GnRH, phosphorylated ERK (pERK) is elevated in 50% of the cells at 1.7 (SD = 0.3) min. Studies of the cell-to-cell response showed that for both pERK and for Egr1 protein production the mean response (μ) and standard deviation (σ) within individual cells were linearly related (σ = kμ) and had similar values of k. To understand the basis for the scaling observed for noise propagation through this system, we determined the relationship between pERK and egr1 mRNA levels induced at varying concentration of GnRH. While both pERK and egr1 mRNA show a saturating sigmoidal relationship to the concentration of GnRH exposure, egr1 mRNA is linearly related to the levels of pERK. These results explain the basis for variation in cellular responses in an important mammalian signaling pathway leading to gene induction. 相似文献
149.
Lalaoui N Morlé A Mérino D Jacquemin G Iessi E Morizot A Shirley S Robert B Solary E Garrido C Micheau O 《PloS one》2011,6(5):e19679
Background
TRAIL/Apo2L is a pro-apoptotic ligand of the TNF family that engages the apoptotic machinery through two pro-apoptotic receptors, TRAIL-R1 and TRAIL-R2. This cell death program is tightly controlled by two antagonistic receptors, TRAIL-R3 and TRAIL-R4, both devoid of a functional death domain, an intracellular region of the receptor, required for the recruitment and the activation of initiator caspases. Upon TRAIL-binding, TRAIL-R4 forms a heteromeric complex with the agonistic receptor TRAIL-R2 leading to reduced caspase-8 activation and apoptosis.Methodology/Principal Findings
We provide evidence that TRAIL-R4 can also exhibit, in a ligand independent manner, signaling properties in the cervical carcinoma cell line HeLa, through Akt. Ectopic expression of TRAIL-R4 in HeLa cells induced morphological changes, with cell rounding, loss of adherence and markedly enhanced cell proliferation in vitro and tumor growth in vivo. Disruption of the PI3K/Akt pathway using the pharmacological inhibitor , siRNA targeting the p85 regulatory subunit of phosphatidylinositol-3 kinase, or by PTEN over-expression, partially restored TRAIL-mediated apoptosis in these cells. Moreover, the Akt inhibitor, LY294002, restituted normal cell proliferation index in HeLa cells expressing TRAIL-R4. LY294002Conclusions/Significance
Altogether, these results indicate that, besides its ability to directly inhibit TRAIL-induced cell death at the membrane, TRAIL-R4 can also trigger the activation of signaling pathways leading to cell survival and proliferation in HeLa cells. Our findings raise the possibility that TRAIL-R4 may contribute to cervical carcinogenesis. 相似文献150.
Alessandra Solari Andrea Giordano Jurgen Kasper Jelena Drulovic An van Nunen Liina Vahter Frederique Viala Erika Pietrolongo Maura Pugliatti Carlo Antozzi Davide Radice Sascha K?pke Christoph Heesen 《PloS one》2013,8(6)