全文获取类型
收费全文 | 849篇 |
免费 | 48篇 |
出版年
2024年 | 1篇 |
2023年 | 7篇 |
2022年 | 24篇 |
2021年 | 30篇 |
2020年 | 11篇 |
2019年 | 16篇 |
2018年 | 22篇 |
2017年 | 22篇 |
2016年 | 30篇 |
2015年 | 42篇 |
2014年 | 51篇 |
2013年 | 57篇 |
2012年 | 88篇 |
2011年 | 69篇 |
2010年 | 44篇 |
2009年 | 38篇 |
2008年 | 54篇 |
2007年 | 47篇 |
2006年 | 41篇 |
2005年 | 52篇 |
2004年 | 43篇 |
2003年 | 31篇 |
2002年 | 31篇 |
2001年 | 3篇 |
2000年 | 7篇 |
1999年 | 1篇 |
1998年 | 10篇 |
1997年 | 5篇 |
1996年 | 3篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1985年 | 1篇 |
1983年 | 1篇 |
排序方式: 共有897条查询结果,搜索用时 78 毫秒
221.
Viviana Madrid Hctor Del Zotto Brbara Maiztegui María A. Raschia María E. Alzugaray Antonio C. Boschero Helena C. Barbosa Luis E. Flores María I. Borelli Juan J. Gagliardino 《Regulatory peptides》2009,157(1-3):25-31
The effect of islet neogenesis-associated protein pentadecapeptide (INGAP-PP) administration to normal male hamsters upon serum glucose and triglyceride levels, β-cell mass and function was studied. INGAP-PP (500 μg) or saline was injected twice daily during 10 days. Both groups showed comparable body weight, serum glucose and triglyceride levels. INGAP-PP treated animals had significantly higher HOMA-IR and HOMA-β and their islets released more insulin in response to glucose; they had lower islet DNA content, significantly increased number of islets/unit area, β-cell replication rate and mass, cells co-expressing Pdx-1/INGAP and islets in contact with ducts, and decreased β-cell apoptosis rate. The percentage of cells expressing Pdx-1 alone or together with INGAP or insulin increased significantly in ducts. These animals also showed a significantly higher concentration of Pdx-1 and Ngn-3 mRNA and a lower number of INGAP-positive cells. In conclusion, INGAP-PP promoted a controlled and functionally active increase of β-cell mass; our data demonstrate for the first time the mechanism responsible for such changes; that Ngn-3 would be involved in INGAP-PP-induced neogenesis; and the existence of a negative feedback loop with endogenous INGAP-producing cells. Accordingly, INGAP-PP could be used to induce these effects in people with or at risk of developing diabetes. 相似文献
222.
Cinzia Di Pietro Marco Ragusa Davide Barbagallo Laura R Duro Maria R Guglielmino Alessandra Majorana Rosario Angelica Marina Scalia Luisa Statello Loredana Salito Luisa Tomasello Salvo Pernagallo Salvo Valenti Vito D'Agostino Patrizio Triberio Igor Tandurella Giuseppe A Palumbo Piera La Cava Viviana Cafiso Taschia Bertuccio Maria Santagati Giovanni Li Destri Salvatore Lanzafame Francesco Di Raimondo Stefania Stefani Bud Mishra Michele Purrello 《BMC medical genomics》2009,2(1):1-35
223.
224.
Eukaryotic initiation factor 6 mediates a continuum between 60S ribosome biogenesis and translation 下载免费PDF全文
Eukaryotic ribosome biogenesis and translation are linked processes that limit the rate of cell growth. Although ribosome biogenesis and translation are mainly controlled by distinct factors, eukaryotic initiation factor 6 (eIF6) has been found to regulate both processes. eIF6 is a necessary protein with a unique anti‐association activity, which prevents the interaction of 40S ribosomal subunits with 60S subunits through its binding to 60S ribosomes. In the nucleolus, eIF6 is a component of the pre‐ribosomal particles and is required for the biogenesis of 60S subunits, whereas in the cytoplasm it mediates translation downstream from growth factors. The translational activity of eIF6 could be due to its anti‐association properties, which are regulated by post‐translational modifications; whether this anti‐association activity is required for the biogenesis and nuclear export of ribosomes is unknown. eIF6 is necessary for tissue‐specific growth and oncogene‐driven transformation, and could be a new rate‐limiting step for the initiation of translation. 相似文献
225.
Antitumor activity of some natural flavonoids and synthetic derivatives on various human and murine cancer cell lines 总被引:7,自引:0,他引:7
The effect of various natural flavonoids, cinnamic acid derivatives, and a series of synthetic flavones on cell proliferation was evaluated in vitro in a panel of established human and murine tumor cell lines. The most potent antiproliferative agents were caffeic acid n-butyl ester (12) > 2'-nitroflavone (26) > caffeic acid ethyl ester (11) approximately = 2',6-dinitroflavone (27) > apigenin (3) > 3'-bromoflavone (20) approximately = 2'-fluoro-6-bromoflavone (31). Some compounds showed a moderate effect, the order of cytotoxic activities being chrysin (2) > 2'-fluoro-6-chloroflavone (30) approximately = 2'-chlorochrysin (32) > alpha-naphthoflavone (7) > beta-naphthoflavone (8) approximately = 6-chloroflavone (14) approximately = 6-bromoflavone (15) approximately = 4'-nitroflavone (23). A structure-activity relationship analysis of each group of compounds was performed. None of the natural or synthetic compounds tested affected the proliferation of epithelial cells derived from normal mammary gland of mice or fibroblastic cells from mouse embryo, suggesting a selective action against tumor cells. 相似文献
226.
Adam B. Salmon Arlan Richardson Viviana I. Pérez 《Free radical biology & medicine》2010,48(5):642-655
The oxidative stress theory of aging predicts that manipulations that alter oxidative stress/damage will alter aging. The gold standard for determining whether aging is altered is life span, i.e., does altering oxidative stress/damage change life span? Mice with genetic manipulations in their antioxidant defense system designed to directly address this prediction have, with few exceptions, shown no change in life span. However, when these transgenic/knockout mice are tested using models that develop various types of age-related pathology, they show alterations in progression and/or severity of pathology as predicted by the oxidative stress theory: increased oxidative stress accelerates pathology and reduced oxidative stress retards pathology. These contradictory observations might mean that (a) oxidative stress plays a very limited, if any, role in aging but a major role in health span and/or (b) the role that oxidative stress plays in aging depends on environment. In environments with minimal stress, as expected under optimal husbandry, oxidative damage plays little role in aging. However, under chronic stress, including pathological phenotypes that diminish optimal health, oxidative stress/damage plays a major role in aging. Under these conditions, enhanced antioxidant defenses exert an “antiaging” action, leading to changes in life span, age-related pathology, and physiological function as predicted by the oxidative stress theory of aging. 相似文献
227.
Moresi V Williams AH Meadows E Flynn JM Potthoff MJ McAnally J Shelton JM Backs J Klein WH Richardson JA Bassel-Duby R Olson EN 《Cell》2010,143(1):35-45
Maintenance of skeletal muscle structure and function requires innervation by motor neurons, such that denervation causes muscle atrophy. We show that myogenin, an essential regulator of muscle development, controls neurogenic atrophy. Myogenin is upregulated in skeletal muscle following denervation and regulates expression of the E3 ubiquitin ligases MuRF1 and atrogin-1, which promote muscle proteolysis and atrophy. Deletion of myogenin from adult mice diminishes expression of MuRF1 and atrogin-1 in denervated muscle and confers resistance to atrophy. Mice lacking histone deacetylases (HDACs) 4 and 5 in skeletal muscle fail to upregulate myogenin and also preserve muscle mass following denervation. Conversely, forced expression of myogenin in skeletal muscle of HDAC mutant mice restores muscle atrophy following denervation. Thus, myogenin plays a dual role as both a regulator of muscle development and an inducer of neurogenic atrophy. These findings reveal a specific pathway for muscle wasting and potential therapeutic targets for this disorder. 相似文献
228.
Viviana Cavalca Fabiana Minardi Samuele Scurati Isabella Squellerio Luca Dainese Elena Tremoli Donatella Caruso 《Analytical biochemistry》2010,397(2):168-174
Both F2-isoprostanes (8-iso-PGF2α), a well-known marker of oxidative stress, and thromboxanes A2 (TXA2) are involved in atherosclerosis through LDL oxidation and platelet activation. Different aspects of the pathology can be described by 8-iso-PGF2α and TXA2 so it is important to determine both their concentrations to monitor the disease progression and/or therapy effects. We developed a simple and sensitive method based on liquid chromatography-tandem mass spectrometry, using electrospray ionization in negative-ion mode, for the simultaneous measurement of the concentration of 8-iso-PGF2α and 11-dehydro thromboxane B2 (11-DH-TXB2), a TXA2 metabolite. This method was applied to analyze urine samples collected overnight from 15 atherosclerotic patients, with documented carotid artery sclerosis (CAS), and from 20 controls. The detection limit was 0.097 pg/μL for 8-iso-PGF2α and 0.375 pg/μL for 11-DH-TXB2, with a linear range of 0.78-25 pg/μL; the inter- and intraday imprecision was <5% for both metabolites. These analytes were higher in CAS (P < 0.005 vs controls) and were positively correlated in patients but not in controls, even after adjustment for age and gender (r = 0.60; P = 0.032). This highly sensitive, precise, and rapid method allows for the simultaneous determination of 8-iso-PGF2α and 11-DH-TXB2 in human urine samples in order to evaluate oxidative stress and platelet aggregation. 相似文献
229.
Viviana Sanchez-Torres Thomas K. Wood 《Biochemical and biophysical research communications》2010,401(2):197-202
Extracellular DNA (eDNA) is a structural component of the polymeric matrix of biofilms from different species. Different mechanisms for DNA release have been proposed including lysis of cells, lysis of DNA-containing vesicles, and DNA secretion. Here, a genome-wide screen of 3985 non-lethal mutations was performed to identify genes whose deletion alters eDNA release in Escherichia coli. Deleting nlpI, yfeC, and rna increased eDNA from planktonic cultures while deleting hns and rfaD decreased eDNA production. The lipoprotein NlpI negatively affects eDNA release since the overexpression of nlpI decreases eDNA 16 fold while deleting nlpI increases eDNA threefold. The global regulator H-NS is required for eDNA production since DNA was not detected for the hns mutant and production of H-NS restored eDNA production to wild-type levels. Therefore our results suggest that secretion may play a role in eDNA release in E. coli since the effect of the hns deletion on cell lysis (slight decrease) and membrane vesicles (threefold increase) does not account for the reduction in eDNA. 相似文献
230.
Breast cancer cell survival signal is affected by bergapten combined with an ultraviolet irradiation
Maria Luisa Panno Francesca Giordano Fabrizia Mastroianni Viviana Bartella Saveria Aquila 《FEBS letters》2010,584(11):2321-2326
In this study we have reported that bergapten (B) and bergapten plus UV (PUVA) are able to significantly affect MCF-7, ZR-75 and SKBR-3 breast cancer cell proliferations.B induced a lowering of PI3K/AKT survival signal in MCF-7 cells even in presence of IGF-I stimulation. Furthermore, B and in a higher extent, PUVA up-regulated the p53 mRNA and the protein content. An increased co-association between p21 WAF and proliferating cell nuclear antigen (PCNA) has been observed in PUVA-treated MCF-7 cells, thus inhibiting DNA replication. These results highlight how B, and its photoactivated compound, exert antiproliferative effects and induce apoptotic responses in breast cancer cells. 相似文献