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排序方式: 共有129条查询结果,搜索用时 15 毫秒
31.
Costanza Montagna Rene B. Svensson Monika L. Bayer Salvatore Rizza Emiliano Maiani Ching-Yan Chlo Yeung Giuseppe Filomeni Michael Kjr 《Cell death & disease》2022,13(4)
Tendons are vital collagen-dense specialized connective tissues transducing the force from skeletal muscle to the bone, thus enabling movement of the human body. Tendon cells adjust matrix turnover in response to physiological tissue loading and pathological overloading (tendinopathy). Nevertheless, the regulation of tendon matrix quality control is still poorly understood and the pathogenesis of tendinopathy is presently unsolved. Autophagy, the major mechanism of degradation and recycling of cellular components, plays a fundamental role in the homeostasis of several tissues. Here, we investigate the contribution of autophagy to human tendons’ physiology, and we provide in vivo evidence that it is an active process in human tendon tissue. We show that selective autophagy of the endoplasmic reticulum (ER-phagy), regulates the secretion of type I procollagen (PC1), the major component of tendon extracellular matrix. Pharmacological activation of autophagy by inhibition of mTOR pathway alters the ultrastructural morphology of three-dimensional tissue-engineered tendons, shifting collagen fibrils size distribution. Moreover, autophagy induction negatively affects the biomechanical properties of the tissue-engineered tendons, causing a reduction in mechanical strength under tensile force. Overall, our results provide the first evidence that autophagy regulates tendon homeostasis by controlling PC1 quality control, thus potentially playing a role in the development of injured tendons.Subject terms: Physiology, Cell biology 相似文献
32.
Ballarò C Ceccarelli S Tiveron C Tatangelo L Salvatore AM Segatto O Alemà S 《EMBO reports》2005,6(8):755-761
Although it has been clearly established that negative feedback loops have a fundamental role in the regulation of epidermal growth factor receptor (EGFR) signalling in flies, their role in the regulation of mammalian EGFR has been inferred only recently from in vitro studies. Here, we report on the forced expression of RALT/MIG-6, a negative feedback regulator of ErbB receptors, in mouse skin. A RALT transgene driven by the K14 promoter generated a dose-dependent phenotype resembling that caused by hypomorphic and antimorphic Egfr alleles-that is, wavy coat, curly whiskers and open eyes at birth. Ex vivo keratinocytes from K14-RALT mice showed reduced biochemical and biological responses when stimulated by ErbB ligands. Conversely, knockdown of RALT by RNA interference enhanced ErbB mitogenic signalling. Thus, RALT behaves as a suppressor of EGFR signalling in mouse skin. 相似文献
33.
Luisa Campagnolo Gaetana Costanza Arianna Francesconi Gaetano Arcuri Ilana Moscatelli Augusto Orlandi 《PloS one》2014,9(1)
Background
Sortilin, a member of the Vps10p-domain receptor family, has been demonstrated a key regulator in mediating cellular response to pro-neurotrophins. In the present study, we investigated the role of sortilin in the apoptotic pathway of vascular smooth muscle cells.Methods and Principal Findings
Immunohistochemistry revealed that sortilin was barely detectable in human and rat normal young vessels, while its expression was increased in human fibroatheromatous plaques. Sortilin immunodetection was also marked in the neointima of the rat aorta fifteen days after ballooning. In vitro, rat aortic intimal cells expressed higher sortilin levels than normal media SMCs; sortilin was distributed in the cytoplasm and in correspondence of the cell membrane. After 48 h, pro-nerve growth factor (proNGF) induced the strong dose-dependent increase of intimal cell apoptosis and the accumulation of sortilin protein. ProNGF was a more potent apoptotic inducer than equimolar or even higher concentration of NGF, whereas brain derived neutrotrophic factor was ineffective. Targeted interfering RNA-mediated sortilin reduction counteracted proNGF-induced apoptosis without affecting p75NTR expression. ProNGF-induced apoptosis was associated to NF-κB down-regulation and bax increase. Inhibition of NF-κB activity increased intimal cell apoptosis that did not further increase with the addition of proNGF.Conclusions
Our results indicate that sortilin expression characterizes human atheromatous lesions and rat aortic post-injury neointima, and suggest that sortilin represents an important regulator of proNGF-induced SMC apoptosis and arterial remodeling. 相似文献34.
Allanore Y Saad M Dieudé P Avouac J Distler JH Amouyel P Matucci-Cerinic M Riemekasten G Airo P Melchers I Hachulla E Cusi D Wichmann HE Wipff J Lambert JC Hunzelmann N Tiev K Caramaschi P Diot E Kowal-Bielecka O Valentini G Mouthon L Czirják L Damjanov N Salvi E Conti C Müller M Müller-Ladner U Riccieri V Ruiz B Cracowski JL Letenneur L Dupuy AM Meyer O Kahan A Munnich A Boileau C Martinez M 《PLoS genetics》2011,7(7):e1002091
Systemic sclerosis (SSc) is an orphan, complex, inflammatory disease affecting the immune system and connective tissue. SSc stands out as a severely incapacitating and life-threatening inflammatory rheumatic disease, with a largely unknown pathogenesis. We have designed a two-stage genome-wide association study of SSc using case-control samples from France, Italy, Germany, and Northern Europe. The initial genome-wide scan was conducted in a French post quality-control sample of 564 cases and 1,776 controls, using almost 500 K SNPs. Two SNPs from the MHC region, together with the 6 loci outside MHC having at least one SNP with a P<10−5 were selected for follow-up analysis. These markers were genotyped in a post-QC replication sample of 1,682 SSc cases and 3,926 controls. The three top SNPs are in strong linkage disequilibrium and located on 6p21, in the HLA-DQB1 gene: rs9275224, P = 9.18×10−8, OR = 0.69, 95% CI [0.60–0.79]; rs6457617, P = 1.14×10−7 and rs9275245, P = 1.39×10−7. Within the MHC region, the next most associated SNP (rs3130573, P = 1.86×10−5, OR = 1.36 [1.18–1.56]) is located in the PSORS1C1 gene. Outside the MHC region, our GWAS analysis revealed 7 top SNPs (P<10−5) that spanned 6 independent genomic regions. Follow-up of the 17 top SNPs in an independent sample of 1,682 SSc and 3,926 controls showed associations at PSORS1C1 (overall P = 5.70×10−10, OR:1.25), TNIP1 (P = 4.68×10−9, OR:1.31), and RHOB loci (P = 3.17×10−6, OR:1.21). Because of its biological relevance, and previous reports of genetic association at this locus with connective tissue disorders, we investigated TNIP1 expression. A markedly reduced expression of the TNIP1 gene and also its protein product were observed both in lesional skin tissue and in cultured dermal fibroblasts from SSc patients. Furthermore, TNIP1 showed in vitro inhibitory effects on inflammatory cytokine-induced collagen production. The genetic signal of association with TNIP1 variants, together with tissular and cellular investigations, suggests that this pathway has a critical role in regulating autoimmunity and SSc pathogenesis. 相似文献
35.
36.
37.
Ferroni L Baldisserotto C Giovanardi M Pantaleoni L Morosinotto T Pancaldi S 《Journal of bioenergetics and biomembranes》2011,43(2):163-173
Room temperature (RT) microspectrofluorimetry in vivo of single cells has a great potential in photosynthesis studies. In
order to get new information on RT chlorophyll fluorescence bands, we analyzed the spectra of Chlamydomonas reinhardtii mutants lacking fundamental proteins of the thylakoid membrane and spectra of photoinhibited WT cells. RT spectra of single
living cells were characterized thorough derivative analyses and Gaussian deconvolution. The results obtained suggest that
the dynamism in LHCII assembly could be sufficient to explain the variations in amplitudes of F680 (free LHCII), F694 (LHCII-PSII)
and F702 (LHCII aggregates); F686 was assigned to the PSII core. Based on the revised assignments and on the variations observed,
we discuss the meaning of the two fluorescence emission ratios F680/(F686 + F694) and F702/(F686 + F694), showing that these
are sensitive parameters under moderate photoinhibition. In the most photoinhibited samples, the RT spectra tended to degenerate,
showing characteristics of mutants that are partly depleted in PSII. 相似文献
38.
Costanza Bagnoli Terje Christensen Francesco Lenci Santi Nonell Dennis Paul Valenzeno 《Photochemical & photobiological sciences》2004,3(8):788-794
The DPC offers many benefits for learners, teachers and developers involved in creation of teaching materials in photobiology. Modifications and additions can be made relatively easily. Anonymous peer review of modules, allowing them to be cited as peer reviewed publications, is likely to encourage new submissions. 相似文献
39.
Jiang Zhao Frederick A. Heberle Paul Klawitter Greg Costanza 《生物化学与生物物理学报:生物膜》2007,1768(11):2764-2776
We have undertaken a series of experiments to examine the behavior of individual components of cell membranes. Here we report an initial stage of these experiments, in which the properties of a chemically simple lipid mixture are carefully mapped onto a phase diagram. Four different experimental methods were used to establish the phase behavior of the 3-component mixture DSPC/DOPC/chol: (1) confocal fluorescence microscopy observation of giant unilamellar vesicles, GUVs; (2) FRET from perylene to C20:0-DiI; (3) fluorescence of dilute dyes C18:2-DiO and C20:0-DiI; and (4) wide angle X-ray diffraction. This particular 3-component mixture was chosen, in part, for a high level of immiscibility of the components in order to facilitate solving the phase behavior at all compositions. At 23 °C, a large fraction of the possible compositions for this mixture give rise to a solid phase. A region of 3-phase coexistence of {Lα + Lβ + Lo} was detected and defined based on a combination of fluorescence microscopy of GUVs, FRET, and dilute C20:0-DiI fluorescence. At very low cholesterol concentrations, the solid phase is the tilted-chain phase Lβ′. Most of the phase boundaries have been determined to be within a few percent of the composition. Measurements of the perturbations of the boundaries of this accurate phase diagram could serve as a means to understand the behaviors of a range of added lipids and proteins. 相似文献
40.
Carlo Rinaldi Christopher Grunseich Irina F. Sevrioukova Alice Schindler Iren Horkayne-Szakaly Costanza Lamperti Guida Landouré Marina L. Kennerson Barrington G. Burnett Carsten Bönnemann Leslie G. Biesecker Daniele Ghezzi Massimo Zeviani Kenneth H. Fischbeck 《American journal of human genetics》2012