全文获取类型
收费全文 | 142篇 |
免费 | 7篇 |
专业分类
149篇 |
出版年
2022年 | 2篇 |
2021年 | 1篇 |
2018年 | 2篇 |
2016年 | 6篇 |
2015年 | 6篇 |
2014年 | 5篇 |
2013年 | 5篇 |
2012年 | 19篇 |
2011年 | 7篇 |
2010年 | 9篇 |
2009年 | 7篇 |
2008年 | 9篇 |
2007年 | 11篇 |
2006年 | 2篇 |
2005年 | 3篇 |
2004年 | 12篇 |
2003年 | 6篇 |
2002年 | 9篇 |
2001年 | 2篇 |
1999年 | 1篇 |
1998年 | 1篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1992年 | 1篇 |
1985年 | 1篇 |
1982年 | 1篇 |
1980年 | 3篇 |
1976年 | 1篇 |
1974年 | 2篇 |
1966年 | 1篇 |
1964年 | 1篇 |
1963年 | 2篇 |
1962年 | 1篇 |
1960年 | 1篇 |
1956年 | 1篇 |
1954年 | 1篇 |
排序方式: 共有149条查询结果,搜索用时 0 毫秒
81.
Micol Tillhon Ornella Cazzalini Tiziana Nardo Daniela Necchi Sabrina Sommatis Lucia A. Stivala A. Ivana Scovassi Ennio Prosperi 《DNA Repair》2012,11(10):844-852
Nucleotide excision repair (NER) is an important DNA repair mechanism through which cells remove bulky DNA lesions. Following DNA damage, the histone acetyltransferase (HAT) p300 (also referred to as lysine acetyltransferase or KAT) is known to associate with proliferating cell nuclear antigen (PCNA), a master regulator of DNA replication and repair processes. This interaction, which results in HAT inhibition, may be dissociated by the cell cycle inhibitor p21CDKN1A, thereby restoring p300 activity; however, the role of this protein interplay is still unclear. Here, we report that silencing p300 or its homolog CREB-binding protein (CBP) by RNA interference (RNAi) significantly reduces DNA repair synthesis in human fibroblasts. In addition, we determined whether p300 and CBP may associate with and acetylate specific NER factors such as XPG, the 3′-endonuclease that is involved in the incision/excision step and is known to interact with PCNA. Our results show that p300 and CBP interact with XPG, which has been found to be acetylated in vivo. XPG is acetylated by p300 in vitro, and this reaction is inhibited by PCNA. Knocking down both p300/CBP by RNAi or by chemical inhibition with curcumin greatly reduced XPG acetylation, and a concomitant accumulation of the protein at DNA damage sites was observed. The ability of p21 to bind PCNA was found to regulate the interaction between p300 and XPG, and an abnormal accumulation of XPG at DNA damage sites was also found in p21−/− fibroblasts. These results indicate an additional function of p300/CBP in NER through the acetylation of XPG protein in a PCNA–p21 dependent manner. 相似文献
82.
Replication fork stalling in WRN-deficient cells is overcome by prompt activation of a MUS81-dependent pathway 总被引:1,自引:0,他引:1 下载免费PDF全文
Franchitto A Pirzio LM Prosperi E Sapora O Bignami M Pichierri P 《The Journal of cell biology》2008,183(2):241-252
Failure to stabilize and properly process stalled replication forks results in chromosome instability, which is a hallmark of cancer cells and several human genetic conditions that are characterized by cancer predisposition. Loss of WRN, a RecQ-like enzyme mutated in the cancer-prone disease Werner syndrome (WS), leads to rapid accumulation of double-strand breaks (DSBs) and proliferating cell nuclear antigen removal from chromatin upon DNA replication arrest. Knockdown of the MUS81 endonuclease in WRN-deficient cells completely prevents the accumulation of DSBs after fork stalling. Also, MUS81 knockdown in WS cells results in reduced chromatin recruitment of recombination enzymes, decreased yield of sister chromatid exchanges, and reduced survival after replication arrest. Thus, we provide novel evidence that WRN is required to avoid accumulation of DSBs and fork collapse after replication perturbation, and that prompt MUS81-dependent generation of DSBs is instrumental for recovery from hydroxyurea-mediated replication arrest under such pathological conditions. 相似文献
83.
Maddalena Donzelli Claudia Negri Angelo Mandarino Laura Rossi Ennio Prosperi Isabelle Frouin Rosa Bernardi Alexander Burkle A. Ivana Scovassi 《Journal of molecular histology》1997,29(11):831-837
Cell death by apoptosis was analysed in HeLa cells either treated with the antitumoral drug bleomycin or depleted of growth
factors by long-term culture without medium change. The interference of apoptosis with normal cell cycle progression was followed
by flow cytometry in cells stained with propidium iodide and with antibody to S-phase-related PCNA protein. Bleomycin-treated
cells showed a net accumulation in G2/M phase paralleled by the appearance of material with a subdiploid DNA content. Cells with a subdiploid DNA content were
also present in growth factor-depleted cultures and were shown to derive from all the cell cycle phases. To identify apoptotic
features in HeLa cell cultures, we applied a recently developed assay based on the simultaneous analysis in the single cell
of three parameters, namely chromatin condensation, DNA degradation and poly(ADP-ribose) synthesis. Apoptotic cells were visualized
by sequential reactions: Hoechst staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling assay
and immunoreaction with anti-poly(ADP-ribose) monoclonal antibody. Positive reactions were obtained for cells at different
stages of the apoptotic programme showing condensed nuclei, fragmented chromatin and apoptotic bodies
This revised version was published online in November 2006 with corrections to the Cover Date. 相似文献
84.
Luana Quassinti Daniela Pellegrino Filippo Garofalo Ennio Maccari Massimo Bramucci 《Polar Biology》2009,32(5):673-677
Biochemical parameters of the angiotensin converting enzyme-like activity (ACELA) in the gills of two Antarctic teleosts,
Chionodraco hamatus and Trematomus bernacchii were characterized. Enzymatic activity was revealed following hydrolysis of a specific substrate of angiotensin-converting
enzyme N-[3-(2-furyl)acryloyl]l-phenylalanyl-glycyl-glycine (FAPGG) and metabolites were separated by reverse phase HPLC analysis. The results showed similar
Km values for the substrate FAPGG at 5°C for the two species with an increase of Km value for T. bernacchii at 25°C. The optimum pH value was 8.5 at 25°C and optimum chloride concentrations were about 300 mM. In T. bernacchii the optimum temperature for maximum enzyme activity was 50°C, while maximum activity in C. hamatus occurred at 35°C. Lisinopril was more efficient in inhibiting ACELA in C. hamatus with an I
50 value of 16.83 ± 5.11 nM, compared to an I
50 value of 30.66 ± 5.19 nM in T. bernacchii. In conclusion, it appears that some biochemical parameters of ACELA in C. hamatus differ from those in T. bernacchii, probably due to different ways that the enzyme adapts to the constantly cold temperatures of the animal’s environment. 相似文献
85.
Fulvia Felluga Cristina Forzato Patrizia Nitti Giuliana Pitacco Fabio Prati Ennio Valentin Ennio Zangrando 《Chirality》2012,24(12):1005-1012
(R)‐(+) and (S)‐(?)‐1‐phenylethylamine have been shown to promote highly diastereoselective and complementary enantioselective formal [3 + 2]carbocyclization reactions between 2,3‐butanedione and conjugated nitroalkenes with formation of enantiomerically rich 2‐hydroxy‐3‐nitrocyclopentanone derivatives. The reactions were carried out both in solvent and under solvent‐free conditions. The absolute configurations of the products were assigned by X‐ray and circular dichroism spectra analyses. Chirality 24:1005–1012, 2012. © 2012 Wiley Periodicals, Inc. 相似文献
86.
Mirela Kuka Roberta Baronio Sara Valentini Elisabetta Monaci Alessandro Muzzi Susanna Aprea Ennio De Gregorio Ugo D'Oro 《PloS one》2010,5(7)
Background
Pathogen recognition by dendritic cells (DC) is crucial for the initiation of both innate and adaptive immune responses. Activation of Toll-like Receptors (TLRs) by microbial molecular patterns leads to the maturation of DC, which present the antigen and activate T cells in secondary lymphoid tissues. Cytokine production by DC is critical for shaping the adaptive immune response by regulating T helper cell differentiation. It was previously shown by our group that Src kinases play a key role in cytokines production during TLR4 activation in human DC.Principal Findings
In this work we investigated the role of Src kinases during different TLRs triggering in human monocyte-derived DC (MoDC). We found that Src family kinases are important for a balanced production of inflammatory cytokines by human MoDC upon stimulation of TLR3 and 8 with their respective agonists. Disruption of this equilibrium through pharmacological inhibition of Src kinases alters the DC maturation pattern. In particular, while expression of IL-12 and other inflammatory cytokines depend on Src kinases, the induction of IL-23 and co-stimulatory molecules do not. Accordingly, DC treated with Src inhibitors are not compromised in their ability to induce CD4 T cell proliferation and to promote the Th17 subset survival but are less efficient in inducing Th1 differentiation.Conclusions
We suggest that the pharmacological modulation of DC maturation has the potential to shape the quality of the adaptive immune response and could be exploited for the treatment of inflammation-related diseases. 相似文献87.
Cazzalini O Perucca P Valsecchi F Stivala LA Bianchi L Vannini V Prosperi E 《Histochemistry and cell biology》2004,121(5):377-381
The cyclin-dependent kinase (CDK) inhibitor p21CDKN1A is known to induce cell cycle arrest by inhibiting CDK activity and by interfering with DNA replication through binding to proliferating cell nuclear antigen. Although the molecular mechanisms have been elucidated, the temporal dynamics, as well as the intracellular sites of the activity of p21 bound to cyclin/CDK complexes during cell cycle arrest, have not been fully investigated. In this study we have induced the expression of p21CDKN1A fused to green fluorescent protein (GFP) in HeLa cells, in order to visualize the intracellular localization of the inhibitor during the cell cycle arrest. We show that p21-GFP is preferentially expressed in association with cyclin E in cells arrested in G1 phase, and with cyclin A more than with cyclin B1 in cells arrested in the G2/M compartment. In addition, we show for the first time that p21-GFP colocalizes with cyclin E in the nucleolus of HeLa cells during the G1 phase arrest.O. Cazzalini and P. Perucca contributed equally to this work 相似文献
88.
Cazzalini O Perucca P Riva F Stivala LA Bianchi L Vannini V Ducommun B Prosperi E 《Cell cycle (Georgetown, Tex.)》2003,2(6):596-603
The ability of the cyclin-dependent kinase (CDK) inhibitor p21CDKN1A to interact with PCNA recruited to DNA replication sites was investigated to elucidate the relevance of this interaction in cell cycle arrest. To this end, expression of p21 protein fused to green fluorescent protein (GFP) was induced in HeLa cells. G1 phase cell cycle arrest induced by p21GFP occurred also at the G1/S transition, as shown by cyclin A immunostaining of GFP-positive cells. Confocal microscopy analysis and co-immunoprecipitation studies showed that p21GFP co-localized and interacted with chromatin-bound PCNA and CDK2. GFP-p21 mutant forms unable to bind to PCNA (p21PCNA-) or CDK (p21CDK-) induced cell cycle arrest, although immunoprecipitation experiments showed these mutants to be unstable. Expression of HA-tagged p21wt or mutant proteins confirmed the ability of both mutants to arrest cell cycle. p21(wt)HA and p21CDK-HA, but not p21PCNA-, co-localized and co-immunoprecipitated with chromatin-bound PCNA. Association of p21 to chromatin-bound PCNA resulted in the loss of interaction with the p125 catalytic subunit of DNA polymerase delta (pol delta). These results suggest that in vivo p21 does not interfere with loading of PCNA at DNA replication sites, but prevents, or displaces subsequent binding of pol delta to PCNA at the G1/S phase transition. 相似文献
89.
Preatoni E Colombo A Verga M Galvani C Faina M Rodano R Preatoni E Cardinale M 《Journal of strength and conditioning research / National Strength & Conditioning Association》2012,26(9):2495-2506
The aims of this study were to assess the behavior of a vibrating platform under different conditions and to compare the effects of an 8-week periodized training program with whole-body vibration (WBV) alone or in combination with conventional strength training (ST). Vibrating frequencies, displacements, and peak accelerations were tested through a piezoelectric accelerometer under different conditions of load and subjects' position. Eighteen national-level female athletes were assigned to 1 of 3 different groups performing WBV, conventional ST, or a combination of the 2 (WBV + ST). Isometric maximal voluntary contraction, dynamic maximal concentric force, and vertical jump tests were performed before and after the conditioning program. Vibrating displacements and maximum accelerations measured on the device were not always consistent with their expected values calculated from the display and manufacturers' information (sinusoidal waveforms). The WBV alone or in combination with low-intensity resistance exercise did not seem to induce significant enhancements in force and power when compared with ST. It appears that WBV cannot substitute parts of ST loading in a cohort of young female athletes. However, vibration effects might be limited by the behavior of the commercial platforms as the one used in the study. More studies are needed to analyze the performances of devices and the effectiveness of protocols. 相似文献
90.
Ornella Cazzalini Francesca Donà Monica Savio Micol Tillhon Cristina Maccario Paola Perucca Lucia A. Stivala A. Ivana Scovassi Ennio Prosperi 《DNA Repair》2010,9(6):627-635
The cell cycle inhibitor p21CDKN1A has been shown to participate in nucleotide excision repair by interacting with PCNA. Here we have investigated whether p21 plays a role in base excision repair (BER), by analyzing p21 interactions with BER factors, and by assessing the response of p21?/? human fibroblasts to DNA damage induced by alkylating agents. Absence of p21 protein resulted in a higher sensitivity to alkylation-induced DNA damage, as indicated by reduced clonogenic efficiency, defective DNA repair (assessed by the comet test), and by persistence of histone H2AX phosphorylation. To elucidate the mechanisms at the basis of the function of p21 in BER, we focused on its interaction with poly(ADP-ribose) polymerase-1 (PARP-1), an important player in this repair process. p21 was found to bind the automodification/DNA binding domain of PARP-1, although some interaction occurred also with the catalytic domain after DNA damage. This association was necessary to regulate PARP-1 activity since poly(ADP-ribosylation) induced by DNA damage was higher in p21?/? human fibroblasts than in parental p21+/+ cells, and in primary fibroblasts after p21 knock-down by RNA interference. Concomitantly, recruitment of PARP-1 and PCNA to damaged DNA was greater in p21?/? than in p21+/+ fibroblasts. This accumulation resulted in persistent interaction of PARP-1 with BER factors, such as XRCC1 and DNA polymerase β, suggesting that prolonged association reduced the DNA repair efficiency. These results indicate that p21 regulates the interaction between PARP-1 and BER factors, to promote efficient DNA repair. 相似文献