全文获取类型
收费全文 | 238篇 |
免费 | 23篇 |
出版年
2023年 | 1篇 |
2022年 | 3篇 |
2021年 | 4篇 |
2020年 | 4篇 |
2019年 | 4篇 |
2018年 | 6篇 |
2017年 | 4篇 |
2016年 | 3篇 |
2015年 | 7篇 |
2014年 | 21篇 |
2013年 | 16篇 |
2012年 | 21篇 |
2011年 | 26篇 |
2010年 | 11篇 |
2009年 | 12篇 |
2008年 | 15篇 |
2007年 | 21篇 |
2006年 | 15篇 |
2005年 | 7篇 |
2004年 | 10篇 |
2003年 | 13篇 |
2002年 | 8篇 |
1999年 | 4篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1995年 | 4篇 |
1994年 | 2篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1990年 | 3篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1982年 | 2篇 |
1972年 | 2篇 |
1970年 | 1篇 |
排序方式: 共有261条查询结果,搜索用时 15 毫秒
71.
Domenica Scumaci Francesca Trimboli Ludovica Dell’Aquila Antonio Concolino Giusi Pappaianni Laura Tammè Giorgio Vignola Alessia Luciani Daniela Morelli Giovanni Cuda Andrea Boari Domenico Britti 《PloS one》2015,10(2)
The aim of this study was to shed light in to the complexity of the ovine colostrum proteome, with a specific focus on the low abundance proteins. The ovine colostrum is characterized by a few dominating proteins, as the immunoglobulins, but it also contains less represented protein species, equally important for the correct development of neonates. Ovine colostrum, collected immediately after lambing, was separated by 1D SDS-PAGE. Proteins bands were digested with trypsin and the resulting peptides were analyzed by LC-MS/MS. On the basis of the Swiss-Prot database, a total of 343 unique proteins were identified. To our knowledge, this study represents the most comprehensive analysis of ovine colostrum proteome. 相似文献
72.
Samuele De Minicis Laura Agostinelli Chiara Rychlicki Gian Pio Sorice Stefania Saccomanno Cinzia Candelaresi Andrea Giaccari Luciano Trozzi Irene Pierantonelli Eleonora Mingarelli Marco Marzioni Giovanna Muscogiuri Melania Gaggini Antonio Benedetti Amalia Gastaldelli Maria Guido Gianluca Svegliati-Baroni 《PloS one》2014,9(5)
NAFLD is the most common liver disease worldwide but it is the potential evolution to NASH and eventually to hepatocellular carcinoma (HCC), even in the absence of cirrhosis, that makes NAFLD of such clinical importance. Aim: we aimed to create a mouse model reproducing the pathological spectrum of NAFLD and to investigate the role of possible co-factors in promoting HCC. Methods: mice were treated with a choline-deficient L-amino-acid-defined-diet (CDAA) or its control (CSAA diet) and subjected to a low-dose i.p. injection of CCl4 or vehicle. Insulin resistance was measured by the euglycemic-hyperinsulinemic clamp method. Steatosis, fibrosis and HCC were evaluated by histological and molecular analysis. Results: CDAA-treated mice showed peripheral insulin resistance at 1 month. At 1–3 months, extensive steatosis and fibrosis were observed in CDAA and CDAA+CCl4 groups. At 6 months, equal increase in steatosis and fibrosis was observed between the two groups, together with the appearance of tumor. At 9 months of treatment, the 100% of CDAA+CCl4 treated mice revealed tumor versus 40% of CDAA mice. Insulin-like Growth Factor-2 (IGF-2) and Osteopontin (SPP-1) were increased in CDAA mice versus CSAA. Furthermore, Immunostaining for p-AKT, p-c-Myc and Glypican-3 revealed increased positivity in the tumors. Conclusions: the CDAA model promotes the development of HCC from NAFLD-NASH in the presence of insulin resistance but in the absence of cirrhosis. Since this condition is increasingly recognized in humans, our study provides a model that may help understanding mechanisms of carcinogenesis in NAFLD. 相似文献
73.
Rosanna La Rocca Rossana Tallerico Almosawy Talib Hassan Gobind Das Lakshmikanth Tadepally Marco Matteucci Carlo Liberale Maria Mesuraca Domenica Scumaci Francesco Gentile Gheorghe Cojoc Gerardo Perozziello Antonio Ammendolia Adriana Gallo Klas K?rre Giovanni Cuda Patrizio Candeloro Enzo Di Fabrizio Ennio Carbone 《PloS one》2014,9(12)
In our body, cells are continuously exposed to physical forces that can regulate different cell functions such as cell proliferation, differentiation and death. In this work, we employed two different strategies to mechanically stress cancer cells. The cancer and healthy cell populations were treated either with mechanical stress delivered by a micropump (fabricated by deep X-ray nanolithography) or by ultrasound wave stimuli. A specific down-regulation of Major Histocompatibility Complex (MHC) class I molecules expression on cancer cell membrane compared to different kinds of healthy cells (fibroblasts, macrophages, dendritic and lymphocyte cells) was observed, stimulating the cells with forces in the range of nano-newton, and pressures between 1 and 10 bar (1 bar = 100.000 Pascal), depending on the devices used. Moreover, Raman spectroscopy analysis, after mechanical treatment, in the range between 700–1800 cm−1, indicated a relative concentration variation of MHC class I. PCA analysis was also performed to distinguish control and stressed cells within different cell lines. These mechanical induced phenotypic changes increase the tumor immunogenicity, as revealed by the related increased susceptibility to Natural Killer (NK) cells cytotoxic recognition. 相似文献
74.
Domenica Altavilla Ciro Famulari Maria Passaniti Giuseppe M. Campo Antonio MacrÌ Paolo Seminara 《Free radical research》2013,47(4):425-435
Increased lipid peroxidation, enhanced nuclear factor kappa-B (NF- s B) activation and augmented tumor necrosis factor- f (TNF- f ) production have been implicated in cerulein-induced pancreatitis. We investigated whether lipid peroxidation inhibition might reduce NF- s B activation and the inflammatory response in cerulein-induced pancreatitis. Male Sprague-Dawley rats of 230-250 g body weight received administration of cerulein (80 w g/kg s.c. for each of four injections at hourly intervals). A control group received four s.c. injections of 0.9% saline at hourly intervals. Animals were randomized to receive either raxofelast, an inhibitor of lipid peroxidation (20 mg/kg i.p. administered with the first cerulein injection) or its vehicle (1 ml/kg of a 10% DMSO/NaCl solution). All these rats were sacrificed 2 h after the last injection of either cerulein or its vehicle. Raxofelast administration (20 mg/kg i.p. with the first cerulein) significantly reduced malondialdehyde (MDA) levels, an index of lipid peroxidation (CER+DMSO=3.075 - 0.54 w mol/g; CER+raxofelast= 0.693 - 0.18 w mol/g; p <0.001 ), decreased myeloperoxidase (MPO) activity ( CER+DMSO=22.2 - 3.54 mU/g; CER+raxofelast=9.07 - 2.05 mU/g; p <0.01 ), increased glutathione levels (GSH) (CER+DMSO= 5.21 - 1.79 w mol/g; CER+raxofelast=15.71 - 2.14 w mol/g; p <0.001 ), and reduced acinar cell damage evaluated by means of histology and serum levels of both amylase ( CER+DMSO=4063 - 707.9 U/l; CER+raxofelast=1198 - 214.4 U/l; p <0.001 ), and lipase (CER+DMSO=1654 - 330 U/l; CER+raxofelast= 386 - 118.2 U/l; p <0.001 ), Furthermore, raxofelast reduced pancreatic NF- s B activation and the TNF- f mRNA levels and tissue content of mature protein in the pancreas. Indeed, lipid peroxidation inhibition might be considered a potential therapeutic approach to prevent the severe damage in acute pancreatitis. 相似文献
75.
Claudia Calabrese Marina Mangiulli Caterina Manzari Anna Maria Paluscio Mariano Francesco Caratozzolo Flaviana Marzano Ivana Kurelac Anna Maria D’Erchia Domenica D’Elia Flavio Licciulli Sabino Liuni Ernesto Picardi Marcella Attimonelli Giuseppe Gasparre Anna Maria Porcelli Graziano Pesole Elisabetta Sbisà Apollonia Tullo 《BMC genomics》2013,14(1)
76.
Musumeci D Bucci EM Roviello GN Sapio R Valente M Moccia M Bianchi ME Pedone C 《Molecular bioSystems》2011,7(5):1742-1752
In this work we report the design and synthesis of kinked oligonucleotide duplexes as potential inhibitors of HMGB1, a cytokine which triggers a broad range of immunological effects. We found that the designed ligands can interact with HMGB1, as evidenced by circular dichroism spectroscopy, and are able to block some extracellular effects induced by the protein, such as cellular proliferation and migration, as we demonstrated by in vitro biological assays. After selecting the most stable and active kinked duplex, we synthesized the corresponding PNA/DNA chimeric duplex which resulted to be more resistant to enzymatic degradation, and showed a biological activity comparable to that of the natural duplex. Preliminary in vivo assays in a mouse inflammatory model, showed a significant decrease of the mortality after administration of the PNA/DNA kinked duplex to LPS-treated mice. 相似文献
77.
Beatriz Gonçalves Odrade Nougué Florian Jabbour Céline Ridel Halima Morin Patrick Laufs Domenica Manicacci Catherine Damerval 《The Plant journal : for cell and molecular biology》2013,76(2):223-235
Flower architecture mutants provide a unique opportunity to address the genetic origin of flower diversity. Here we study a naturally occurring floral dimorphism in Nigella damascena (Ranunculaceae), involving replacement of the petals by numerous sepal‐like and chimeric sepal/stamen organs. We performed a comparative study of floral morphology and floral development, and characterized the expression of APETALA3 and PISTILLATA homologs in both morphs. Segregation analyses and gene silencing were used to determine the involvement of an APETALA3 paralog (NdAP3–3) in the floral dimorphism. We demonstrate that the complex floral dimorphism is controlled by a single locus, which perfectly co‐segregates with the NdAP3–3 gene. This gene is not expressed in the apetalous morph and exhibits a particular expression dynamic during early floral development in the petalous morph. NdAP3–3 silencing in petalous plants perfectly phenocopies the apetalous morph. Our results show that NdAP3–3 is fully responsible for the complex N. damascena floral dimorphism, suggesting that it plays a role not only in petal identity but also in meristem patterning, possibly through regulation of perianth organ number and the perianth/stamen boundary. 相似文献
78.
Currò M Marini H Alibrandi A Ferlazzo N Condello S Polito F Adamo EB Atteritano M D'Anna R Altavilla D Bitto A Squadrito F Ientile R Caccamo D 《The Journal of steroid biochemistry and molecular biology》2011,127(3-5):413-417
Multiple factors may contribute to the pathogenesis of postmenopausal osteoporosis including environmental, life-style and genetic factors. Common variants in ESR2 gene encoding for ER-beta, highly expressed in bone tissue, have recently been proposed as candidates for affecting bone phenotype at the population level, particularly in postmenopausal women. In this study, we examined the genetic background at ESR2 AluI (rs4986938, 1730G>A) locus in 89 osteopenic, postmenopausal women (age range 49-56 years) together with BMD at lumbar spine and femoral neck sites as well as variations in plasma levels of bone metabolism and turnover markers. Genotyping for ESR2 G1730A polymorphism showed that the frequency of A mutated allele accounted for 0.4 in our cohort of postmenopausal women; moreover, the GA1730 heterozygous individuals were the most represented (50.6%) compared with GG (37.8%) and AA homozygous ones (14.6%). A regression analysis showed that lumbar spine BMD values were significantly associated with both ESR2 AA1730 genotype (p=0.044) and time since the onset of menopause (p=0.031), while no significant association was detected between biochemical markers and genetic background. Interestingly, 85% of patients with AA1730 genotype presented the smallest lumbar spine BMD values. These findings first indicate a worsening effect of ESR2 AluI polymorphism on lumbar spine BMD reduction in postmenopause, suggesting that the detection of this ESR2 variant should be recommended in postmenopausal women, particularly in populations with a high prevalence of ESR2 AA1730 homozygous genotype. 相似文献
79.
80.