全文获取类型
收费全文 | 937篇 |
免费 | 61篇 |
专业分类
998篇 |
出版年
2023年 | 1篇 |
2022年 | 7篇 |
2021年 | 19篇 |
2020年 | 5篇 |
2019年 | 11篇 |
2018年 | 26篇 |
2017年 | 18篇 |
2016年 | 31篇 |
2015年 | 53篇 |
2014年 | 53篇 |
2013年 | 85篇 |
2012年 | 72篇 |
2011年 | 80篇 |
2010年 | 61篇 |
2009年 | 48篇 |
2008年 | 54篇 |
2007年 | 60篇 |
2006年 | 56篇 |
2005年 | 50篇 |
2004年 | 32篇 |
2003年 | 45篇 |
2002年 | 48篇 |
2001年 | 7篇 |
2000年 | 3篇 |
1999年 | 5篇 |
1998年 | 2篇 |
1997年 | 6篇 |
1996年 | 2篇 |
1995年 | 8篇 |
1994年 | 7篇 |
1993年 | 6篇 |
1992年 | 6篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1989年 | 3篇 |
1988年 | 5篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1985年 | 2篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1974年 | 5篇 |
1967年 | 1篇 |
1966年 | 1篇 |
1965年 | 3篇 |
1964年 | 2篇 |
排序方式: 共有998条查询结果,搜索用时 9 毫秒
11.
Yan G. Ni Jon H. Condra Laura Orsatti Xun Shen Stefania Di Marco Shilpa Pandit Matthew J. Bottomley Lionello Ruggeri Richard T. Cummings Rose M. Cubbon Joseph C. Santoro Anka Ehrhardt Dale Lewis Timothy S. Fisher Sookhee Ha Leila Njimoluh Dana D. Wood Holly A. Hammond Douglas Wisniewski Cinzia Volpari Alessia Noto Paola Lo Surdo Brian Hubbard Andrea Carf�� Ayesha Sitlani 《The Journal of biological chemistry》2010,285(17):12882-12891
12.
13.
Lucia Ciccoli Viviana Rossi Silvia Leoncini Cinzia Signorini Patrizia Paffetti Rodolfo Bracci 《Free radical research》2013,47(1):51-58
Iron is released in a desferrioxamine (DFO)-chelatable form (DCI) when erythrocytes are challenged by an oxidative stress. In g -thalassemic erythrocytes, both DCI content and release (after aerobic incubation for 24 h) are increased and correlated with the fetal hemoglobin (HbF) levels. Since erythrocytes from newborns have an extremely high content of HbF and are exposed to conditions of oxidative stress, the release of iron in these erythrocytes was investigated. The erythrocyte DCI content was increased in preterm but not in term newborns as compared to adults, while the release was increased in both preterm and term erythrocytes. The level of plasma non protein-bound iron (NPBI), which was not detectable in adults, was much higher in preterm than in term newborns. When term plus preterm newborns were divided in two groups, normoxic and hypoxic, according to cord blood pH, it was found that both iron release and NBPI were markedly higher in the hypoxic newborns compared to normoxic ones. Similar results were also obtained when the preterm and term infants were considered separately on the basis of cord blood pH. Therefore, iron release and NPBI are higher when conditions of hypoxia occur. In fact, when the values for iron release and NPBI were separately plotted against cord blood pH values, significant negative correlations were seen in both cases. NPBI was correlated with iron release seen in all the newborns and a significant part of the released iron could be recovered into the incubation medium at the end of the incubation. 相似文献
14.
Silvia Leoncini Viviana Rossi Cinzia Signorini Italo Tanganelli Mario Comporti 《Free radical research》2013,47(8):716-724
Increased oxidative stress and decreased life span of erythrocytes (RBCs) are repeatedly reported in diabetes. In the aim to elucidate the mechanism of the latter, i.e. the events leading to erythrocyte ageing, this study determined in RBCs from diabetic patients iron release in a free desferrioxamine-chelatable form (DCI), methemoglobin (MetHb) formation, binding of autologous IgG to membrane proteins and in plasma non-protein-bound iron (NPBI), F2-Isoprostanes (F2-IsoPs) and advanced oxidation protein products (AOPP). DCI and MetHb were higher in diabetic RBCs than in controls and autologous IgG binding occurred in a much higher percentage of diabetic patients than controls. A significant correlation between DCI and IgG binding was found in diabetic RBCs. Plasma NPBI, esterified F2-IsoPs and AOPP were higher in diabetic patients and a significant correlation was found between plasma NPBI and intra-erythrocyte DCI. The increased DCI and autologous IgG binding appear to be important factors in the accelerated removal of RBCs from the blood stream in diabetes and the increase in plasma NPBI could play an important role in the increased oxidative stress. 相似文献
15.
Cecilia Marini Barbara Salani Michela Massollo Adriana Amaro Alessia Isabella Esposito Anna Maria Orengo Selene Capitanio Laura Emionite Mattia Riondato Gianluca Bottoni Cinzia Massara Simona Boccardo Marina Fabbi Cristina Campi Silvia Ravera Giovanna Angelini Silvia Morbelli Michele Cilli Renzo Cordera Mauro Truini Davide Maggi Ulrich Pfeffer Gianmario Sambuceti 《Cell cycle (Georgetown, Tex.)》2013,12(22):3490-3499
Emerging evidence suggests that metformin, a widely used anti-diabetic drug, may be useful in the prevention and treatment of different cancers. In the present study, we demonstrate that metformin directly inhibits the enzymatic function of hexokinase (HK) I and II in a cell line of triple-negative breast cancer (MDA-MB-231). The inhibition is selective for these isoforms, as documented by experiments with purified HK I and II as well as with cell lysates. Measurements of 18F-fluoro-deoxyglycose uptake document that it is dose- and time-dependent and powerful enough to virtually abolish glucose consumption despite unchanged availability of membrane glucose transporters. The profound energetic imbalance activates phosphorylation and is subsequently followed by cell death. More importantly, the “in vivo” relevance of this effect is confirmed by studies of orthotopic xenografts of MDA-MB-231 cells in athymic (nu/nu) mice. Administration of high drug doses after tumor development caused an evident tumor necrosis in a time as short as 48 h. On the other hand, 1 mo metformin treatment markedly reduced cancer glucose consumption and growth. Taken together, our results strongly suggest that HK inhibition contributes to metformin therapeutic and preventive potential in breast cancer. 相似文献
16.
17.
Luigi Ornano Alessandro Venditti Mauro Ballero Cinzia Sanna Luana Quassinti Massimo Bramucci Giulio Lupidi Fabrizio Papa Sauro Vittori Filippo Maggi Armanodoriano Bianco 《化学与生物多样性》2013,10(8):1464-1474
The essential oils of Artemisia arborescens growing in Sardinia (Italy), collected during three plant growth stages, i.e., from the vegetative stage to post‐blooming time, were characterized. Moreover, the in vitro antiproliferative and antioxidant activities of the oil isolated from aerial parts collected in February were evaluated. The essential oils belonged to the β‐thujone/chamazulene chemotype, notably with the highest amount of chamazulene (ca. 52%) ever detected up to now in the genus Artemisia and, in general, in essential oils. Quantitative variations in the oil composition were observed as the plant passes from the vegetative to the blooming stage. The oil was tested for its potential tumor cell growth‐inhibitory effect on T98G, MDA‐MB 435S, A375, and HCT116 human cell lines, using the MTT (=3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide) assay. The highest activity was observed on A375 and HCT116 cell lines, with IC50 values of 14 μg/ml. Moreover, the in vitro antioxidant and free radical‐scavenging assays revealed the oil to be an effective scavenger of the ABTS radical cation, with an activity comparable to that of Trolox®. These results support the use of A. arborescens oil for the treatment of inflamed skin conditions. Finally, the composition of the polar fraction of the A. arborescens aerial parts was also examined, and the main component detected was 5‐O‐caffeoylquinic acid, which was identified for the first time in this plant. 相似文献
18.
Ilda D'Annessa Cinzia Tesauro Zhenxing Wang Barbara Arnò Laura Zuccaro Paola Fiorani Alessandro Desideri 《Biochimica et Biophysica Acta - Proteins and Proteomics》2013,1834(12):2712-2721
Human topoisomerase 1B, the unique target of the natural anticancer compound camptothecin, catalyzes the unwinding of supercoiled DNA by introducing transient single strand nicks and providing covalent protein–DNA adducts. The functional properties and the drug reactivity of the single Arg634Ala mutant have been investigated in comparison to the wild type enzyme. The mutant is characterized by an identical relaxation and cleavage rate but it displays resistance to camptothecin as indicated by a viability assay of the yeast cells transformed with the mutated protein. The mutant also displays a very fast religation rate that is only partially reduced by the presence of the drug, suggesting that this is the main reason for its resistance. A comparative analysis of the structural–dynamical properties of the native and mutant proteins by molecular dynamics simulation indicates that mutation of Arg634 brings to a loss of motion correlation between the different domains and in particular between the linker and the C-terminal domain, containing the catalytic tyrosine residue. These results indicate that the loss of motion correlation and the drug resistance are two strongly correlated events. 相似文献
19.
Adriano Redler Giorgio Di Rocco Domenico Giannotti Francesca Frezzotti Maria Giulia Bernieri Simona Ceccarelli Sirio D’Amici Enrica Vescarelli Anna Paola Mitterhofer Antonio Angeloni Cinzia Marchese 《PloS one》2013,8(8)
Fibroblast growth factor receptor-2 (FGFR-2) plays an important role in tumorigenesis. In thyroid cancer it has been observed a FGFR-2 down-modulation, but the role of this receptor has not been yet clarified. Therefore, we decided to examine the expression of both FGFR-2 isoform, FGFR-2-IIIb and FGFR-2-IIIc, in different histological thyroid variants such as hyperplasia, follicular adenoma and papillary carcinoma. Immunohistochemistry and quantitative Real-Time PCR analyses were performed on samples of hyperplasia, follicular adenoma and papillary carcinoma, compared with normal thyroid tissue. Thyroid hyperplasia did not show statistically significant reduction in FGFR-2 protein and mRNA levels. Interestingly, in both follicular adenoma and papillary carcinoma samples we observed a strongly reduced expression of both FGFR-2 isoforms. We speculate that FGFR-2 down-modulation might be an early event in thyroid carcinogenesis. Furthermore, we suggest the potential use of FGFR-2 as an early marker for thyroid cancer diagnosis. 相似文献
20.
Nicola Maruotti Addolorata Corrado Cinzia Rotondo Francesco Paolo Cantatore 《Journal of cellular physiology》2020,235(3):1915-1920
Janus kinases (JAKs) play a pleiotropic role in several important physiological processes, such as cell maturation, cell proliferation, and cell death, via providing transmission signals from several molecules, such as cytokines, interferons, hormones, and growth factors, to the nucleus. Bone physiology and remodeling are markedly influenced by proinflammatory cytokines. Among them, interleukin-1 (IL-1) and IL-6 are considered potent stimulator of bone resorption. Several cytokine receptors, such as IL-6 receptors, are characterized by tyrosine kinases of the JAK family associated with their intracellular domains. There is an emerging interest in the effects of JAKs inhibition on the cells involved in bone remodeling. JAK inhibitors represent a new class of molecules involved in the therapy of numerous immune-mediated inflammatory diseases. In this review, we want to focus on the role of JAKs inhibitors on bone remodeling and on RANKL-RANK-OPG signal and inflammatory cytokines which are involved in the regulation of bone cells, such as osteoblasts and osteoclasts. 相似文献