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81.
Anti‐Inflammatory/Tissue Repair Macrophages Enhance the Cartilage‐Forming Capacity of Human Bone Marrow‐Derived Mesenchymal Stromal Cells 下载免费PDF全文
82.
Francesca M Spagnoli 《The EMBO journal》2015,34(13):1740-1742
Recent research has made important progress in the directed differentiation of human pluripotent stem cells into insulin‐producing beta‐like cells in vitro. A new study published in this issue of The EMBO Journal reports that timely induction of NEUROG3 expression in pancreatic progenitors is a crucial checkpoint for generation of functional human beta cells. 相似文献
83.
Spagnoli A O'Rear L Chandler RL Granero-Molto F Mortlock DP Gorska AE Weis JA Longobardi L Chytil A Shimer K Moses HL 《The Journal of cell biology》2007,177(6):1105-1117
Despite its clinical significance, joint morphogenesis is still an obscure process. In this study, we determine the role of transforming growth factor beta (TGF-beta) signaling in mice lacking the TGF-beta type II receptor gene (Tgfbr2) in their limbs (Tgfbr2(PRX-1KO)). In Tgfbr2(PRX-1KO) mice, the loss of TGF-beta responsiveness resulted in the absence of interphalangeal joints. The Tgfbr2(Prx1KO) joint phenotype is similar to that in patients with symphalangism (SYM1-OMIM185800). By generating a Tgfbr2-green fluorescent protein-beta-GEO-bacterial artificial chromosome beta-galactosidase reporter transgenic mouse and by in situ hybridization and immunofluorescence, we determined that Tgfbr2 is highly and specifically expressed in developing joints. We demonstrated that in Tgfbr2(PRX-1KO) mice, the failure of joint interzone development resulted from an aberrant persistence of differentiated chondrocytes and failure of Jagged-1 expression. We found that TGF-beta receptor II signaling regulates Noggin, Wnt9a, and growth and differentiation factor-5 joint morphogenic gene expressions. In Tgfbr2(PRX-1KO) growth plates adjacent to interphalangeal joints, Indian hedgehog expression is increased, whereas Collagen 10 expression decreased. We propose a model for joint development in which TGF-beta signaling represents a means of entry to initiate the process. 相似文献
84.
85.
T Girard D Cavagna E Padovan G Spagnoli A Urwyler F Zorzato S Treves 《The Journal of biological chemistry》2001,276(51):48077-48082
Malignant hyperthermia (MH) is a pharmacogenetic disease triggered by volatile anesthetics and succinylcholine in genetically predisposed individuals. The underlying feature of MH is a hypersensitivity of the calcium release machinery of the sarcoplasmic reticulum, and in many cases this is a result of point mutations in the skeletal muscle ryanodine receptor calcium release channel (RYR1). RYR1 is mainly expressed in skeletal muscle, but a recent report demonstrated the existence of this isoform in human B-lymphocytes. As B-cells can produce a number of cytokines, including endogenous pyrogens, we investigated whether some of the symptoms seen during MH could be related to the involvement of the immune system. Our results show that (i) Epstein-Barr virus-immortalized B-cells from MH-susceptible individuals carrying the V2168M RYR1 gene mutation were more sensitive to the RYR activator 4-chloro-m-cresol and (ii) their peripheral blood leukocytes produce more interleukin (IL)-1beta after treatment with the RYR activators caffeine and 4-chloro-m-cresol, compared with cells from healthy controls. Our result demonstrate that RYR1-mediated calcium signaling is involved in release of IL-1beta from B-lymphocytes and suggest that some of the symptoms seen during an MH episode may be due to IL-1beta production. 相似文献
86.
Augusto Orlandi Hiroyuki Hao Amedeo Ferlosio Sophie Clément Seiichi Hirota Luigi Giusto Spagnoli Giulio Gabbiani Christine Chaponnier 《Differentiation; research in biological diversity》2009
In the adult heart, cardiac muscle comprises the working myocardium and the conduction system (CS). The latter includes the sinoatrial node (SAN), the internodal tract or bundle (IB), the atrioventricular node (AVN), the atrioventricular bundle (AVB), the bundle branches (BB) and the peripheral Purkinje fibers (PF). Most of the information concerning the phenotypic features of CS tissue derives from the characterization of avian and rodent developing hearts; data concerning the expression of actin isoforms in adult CS cardiomyocytes are scarce. Using specific antibodies, we investigated the distribution of α-skeletal (α-SKA), α-cardiac (α-CA), α-smooth muscle (α-SMA) actin isoforms and other muscle-typical proteins in the CS of human and rat hearts at different ages. SAN and IB cardiomyocytes were characterized by the presence of α-SMA, α-CA, calponin and caldesmon, whereas α-SKA and vimentin were absent. Double immunofluorescence demonstrated the co-localisation of α-SMA and α-CA in I-bands of SAN cardiomyocytes. AVN, AVB, BB and PF cardiomyocytes were α-SMA, calponin, caldesmon and vimentin negative, and α-CA and α-SKA positive. No substantial differences in actin isoform distribution were observed in human and rat hearts, except for the presence of isolated subendocardial α-SMA positive cardiomyocytes co-expressing α-CA in the ventricular septum of the rat. Aging did not influence CS cardiomyocyte actin isoform expression profile. These findings support the concept that cardiomyocytes of SAN retain the phenotype of a developing myogenic cell throughout the entire life span. 相似文献
87.
The phosphorescence from enzyme-generated and -protected triplet acetone is very efficiently quenched by dyes intercalated into DNA. The process is unlikely to be due to energy transfer and is tentatively ascribed to electron transfer occurring within the DNA helix complex with the acting enzyme. This quenching markedly protects DNA from breaks induced by triplet acetone. In the case of some barely emissive enzyme-generated triplet carbonyl species, it is possible to detect a weak emission resulting from the interaction with dye X DNA; this emission may be associated with back electron transfer. 相似文献
88.
Peter Jantscheff Richard Herrmann Giulio Spagnoli Jürgen Reuter Majid Mehtali Michael Courtney Christoph Rochlitz 《Cancer immunology, immunotherapy : CII》1999,48(6):321-330
Eleven patients with advanced cancer were treated in a clinical gene therapy trial by repeated intra- tumoral injections
with different doses of xenogenic fibroblasts secreting high amounts of human interleukin-2 (Vero-IL2). Treatments in a total
of 14 courses were well tolerated and resulted in clinical responses and measurable biological effects. Together with increases
in serum interleukin-2 (IL-2), modifications of the V-β T cell receptor repertoire and induction of intratumoral T-cell infiltration
were observed. When the intratumoral expression of endogenous cytokine genes and the persistence of the IL-2 transgene at
the application site and in peripheral blood were investigated, rapid disappearance of the transgene at the application site
appeared to be the most prominent biological effect. Tests detecting a single Vero-IL2 cell against a background of 105 non-transfected cells were not able to demonstrate significant expression of exogenous IL-2 (i.e. the transgene or transgene-carrying
cells) in tumor biopsies or blood at different times. Therefore, further studies were performed to evaluate the mechanism(s)
involved in the rapid disappearance of xenogenic carrier cells in more detail. We show here that significant in vitro cytotoxicity
against transgene-carrying Vero cells can be observed in peripheral blood of all the patients before treatment as well as
in healthy controls. “Cold” target inhibition shows that significant killing of Vero-IL2 cells is mediated by natural killer
(NK) cells. This was confirmed by showing that established CD3−/CD16
+
/CD56
+
peripheral blood NK cell clones kill both K562 and Vero-IL2 target cells. The failure of other mechanisms (complement, antibody-dependent
cell cytotoxicity or cytotoxic T lymphocytes) to destroy xenogenic, histoincompatible Vero cells in vitro suggests that NK
cells also might be responsible for the killing of Vero-IL2 in vivo and for the failure to detect the transgene at the application
site. These results might also be of importance for some aspects of the current discussion of xenotransplantation.
Received: 9 April 1999 / Accepted: 14 June 1999 相似文献
89.
A Mackensen S Wittnebel H Veelken C Noppen G C Spagnoli A Lindermann 《European cytokine network》1999,10(3):329-336
Human melanoma cell lines may induce a specific T cell response against tumor cells in vitro. However, after repeated restimulation with autologous tumor cells, expansion of CTL is limited and often apoptosis of the T cells occurs. In order to improve conditions inducing primary T cell responses and thus allowing further expansion of tumor specific T cells for an adoptive transfer, we transfected human melanoma cells with the B7.1 gene (CD80), known to be a potent costimulatory molecule for T cell activation. CD80 expression on melanoma cells resulted in improved primary T cell activation, especially of CD8+ T cells. Furthermore, restimulation with CD80+ tumor cells gave rise to long term proliferating CD8+ T cell lines demonstrating an 100-fold expansion of T cells compared to the 20-30-fold increased numbers obtained with the controls (parental tumor cells +/- anti-CD28). T cells stimulated with CD80+ melanoma cells were found to display a MHC class I-restricted cytotoxic activity against the autologous tumor cells. In conclusion, these studies demonstrate the requirement of costimulation in generating large numbers of tumor specific T cells in vitro that may be used for an adoptive transfer in tumor immunotherapy. 相似文献
90.
Adams S Greeder L Reich E Shao Y Fosina D Hanson N Tassello J Singh B Spagnoli GC Demaria S Jungbluth AA 《Cancer immunology, immunotherapy : CII》2011,60(7):999-1007