全文获取类型
收费全文 | 2771篇 |
免费 | 201篇 |
专业分类
2972篇 |
出版年
2023年 | 9篇 |
2022年 | 21篇 |
2021年 | 39篇 |
2020年 | 31篇 |
2019年 | 31篇 |
2018年 | 57篇 |
2017年 | 52篇 |
2016年 | 86篇 |
2015年 | 109篇 |
2014年 | 130篇 |
2013年 | 207篇 |
2012年 | 205篇 |
2011年 | 178篇 |
2010年 | 140篇 |
2009年 | 133篇 |
2008年 | 179篇 |
2007年 | 175篇 |
2006年 | 171篇 |
2005年 | 131篇 |
2004年 | 160篇 |
2003年 | 117篇 |
2002年 | 126篇 |
2001年 | 27篇 |
2000年 | 20篇 |
1999年 | 35篇 |
1998年 | 30篇 |
1997年 | 26篇 |
1996年 | 22篇 |
1995年 | 32篇 |
1994年 | 18篇 |
1993年 | 24篇 |
1992年 | 21篇 |
1991年 | 16篇 |
1990年 | 27篇 |
1989年 | 18篇 |
1988年 | 10篇 |
1987年 | 9篇 |
1986年 | 6篇 |
1985年 | 12篇 |
1984年 | 12篇 |
1983年 | 14篇 |
1982年 | 11篇 |
1981年 | 22篇 |
1980年 | 11篇 |
1979年 | 6篇 |
1978年 | 10篇 |
1977年 | 7篇 |
1976年 | 9篇 |
1974年 | 12篇 |
1973年 | 4篇 |
排序方式: 共有2972条查询结果,搜索用时 15 毫秒
991.
Alessio Molfino Gianfranco Gioia Filippo Rossi Fanelli Maurizio Muscaritoli 《Amino acids》2013,45(6):1273-1292
Beta-hydroxy-beta-methylbutyrate (HMB), a metabolite of the branched-chain amino acid leucine, is extensively used by athletes and bodybuilders in order to increase strength, muscle mass and exercise performance. We performed a systematic review of the clinical literature on the effectiveness of HMB supplementation in healthy and pathological conditions (i.e. training programs, aging, acute and chronic diseases, and after bariatric surgery). We reviewed all clinical trials indexed in Medline that tested HMB supplementation as well as all the experimental data regarding HMB intracellular mechanisms of action. Search terms included: randomized controlled trials, controlled clinical trials, single- and double-blind method, HMB, proteolytic pathways, muscle atrophy, cachexia, and training. We found out 13 studies testing HMB in healthy young trained subjects, 11 in healthy young untrained subjects, 9 in patients affected by chronic diseases (i.e. cancer, HIV, chronic obstructive pulmonary disease), and 6 in elderly subjects. The indexed studies support that HMB is effective in preventing exercise-related muscle damage in healthy trained and untrained individuals as well as muscle loss during chronic diseases. Most of the selected studies showed the effectiveness of HMB in preventing exercise-related muscle damage in healthy trained and untrained individuals as well as muscle loss during chronic diseases. The usual dose of 3 g/day may be routinely recommended to maintain or improve muscle mass and function in health and disease. The safety profile of HMB is unequivocal. Further, well-designed clinical studies are needed to confirm effectiveness and mode of action of HMB, particularly in pathological conditions. 相似文献
992.
Elisabetta Gianazza Cristina Sensi Ivano Eberini Federica Gilardi Marco Giudici Maurizio Crestani 《Amino acids》2013,44(3):1001-1008
To investigate the influence of diet on serum protein pattern, mice were fed for 8 weeks either control chow or a high-fat diet (containing 21 % w/w milk fat and 0.2 % w/w cholesterol); sera were collected and analyzed by 2-DE. The main positive acute-phase reactant proteins, haptoglobin and hemopexin, were significantly up-regulated in animals receiving the high-fat diet. Data on all other proteins also pointed to an inflammatory condition in these animals. The largest change in concentration was observed for carboxylesterase N, a circulating enzyme seldom connected with lipid metabolism in earlier reports. These observations agree with the notion of a link between diet-induced hyperlipidemia and the inflammatory component of its cardiovascular sequels in humans, but the effects in the experimental animals are massive and obviously affect most of the major serum proteins. 相似文献
993.
Toshiko Miyake Maurizio Bruschi Ugo Cosentino Carole Baffert Vincent Fourmond Christophe Léger Giorgio Moro Luca De Gioia Claudio Greco 《Journal of biological inorganic chemistry》2013,18(6):693-700
[FeFe] hydrogenases are H2-evolving enzymes that feature a diiron cluster in their active site (the [2Fe]H cluster). One of the iron atoms has a vacant coordination site that directly interacts with H2, thus favoring its splitting in cooperation with the secondary amine group of a neighboring, flexible azadithiolate ligand. The vacant site is also the primary target of the inhibitor O2. The [2Fe]H cluster can span various redox states. The active-ready form (Hox) attains the FeIIFeI state. States more oxidized than Hox were shown to be inactive and/or resistant to O2. In this work, we used density functional theory to evaluate whether azadithiolate-to-iron coordination is involved in oxidative inhibition and protection against O2, a hypothesis supported by recent results on biomimetic compounds. Our study shows that Fe–N(azadithiolate) bond formation is favored for an FeIIFeII active-site model which disregards explicit treatment of the surrounding protein matrix, in line with the case of the corresponding FeIIFeII synthetic system. However, the study of density functional theory models with explicit inclusion of the amino acid environment around the [2Fe]H cluster indicates that the protein matrix prevents the formation of such a bond. Our results suggest that mechanisms other than the binding of the azadithiolate nitrogen protect the active site from oxygen in the so-called H ox inact state. 相似文献
994.
995.
Maurizio Franzini Xiaocong M. Ye Marc Adler Danielle L. Aubele Albert W. Garofalo Shawn Gauby Erich Goldbach Gary D. Probst Kevin P. Quinn Pam Santiago Hing L. Sham Danny Tam Anh Truong Zhao Ren 《Bioorganic & medicinal chemistry letters》2013,23(7):1967-1973
Leucine-rich repeat kinase 2 (LRRK2) has been implicated in the pathogenesis of Parkinson’s disease (PD). Inhibition of LRRK2 kinase activity is a therapeutic approach that may lead to new treatments for PD. Herein we report the discovery of a series of [1,2,4]triazolo[4,3-b]pyridazines that are potent against both wild-type and mutant LRRK2 kinase activity in biochemical assays and show an unprecedented selectivity towards the G2019S mutant. A structural rational for the observed selectivity is proposed. 相似文献
996.
Guarino Francesco Cellura Maurizio Traverso Marzia 《The International Journal of Life Cycle Assessment》2020,25(10):2063-2085
The International Journal of Life Cycle Assessment - Life cycle sustainability assessment (LCSA) is one of the most relevant tools delving in sustainability science, based currently on the triple... 相似文献
997.
Jason G. Bragg Peter Cuneo Ahamad Sherieff Maurizio Rossetto 《Molecular ecology resources》2020,20(1):54-65
Translocations of threatened species can reduce the risk of extinction from a catastrophic event. For plants, translocation consists of moving individuals, seeds, or cuttings from a native (source) population to a new site. Ideally a translocation population would be genetically diverse and consist of fit founding individuals. In practice, there are challenges to designing such a population, including constraints on the availability of material, and tradeoffs between different goals. Here, we present an approach for designing a translocation population that identifies sets of founders that are optimized according to multiple criteria (e.g., genetic diversity), while also conforming to constraints on the representation of different founders (e.g., propagation success). It uses flexible inputs, including SNP genotypes, matrices of similarity between individuals, and vectors of phenotype data. We apply the approach to a critically endangered plant, Hibbertia puberula subsp. glabrescens (Dilleniaceae), which was genotyped at thousands of SNP loci. The goals of minimizing genetic similarity among the founding individuals and maximizing genetic diversity were largely complementary: populations optimized for one of these criteria were near‐optimal for the other. We also performed analyses in which we minimized genetic similarity among founding individuals while imposing selection (against hypothetical deleterious alleles, and against undesirable phenotypes, respectively), and here characterized sharp tradeoffs. This was useful in allowing the benefits of selection to be weighed against costs in terms of genetic similarity. In summary, we present an approach for designing a translocation population that allows flexible inputs, the imposition of realistic constraints, and examination of conflicting goals. 相似文献
998.
Aleffi S Navari N Delogu W Galastri S Novo E Rombouts K Pinzani M Parola M Marra F 《American journal of physiology. Gastrointestinal and liver physiology》2011,301(2):G210-G219
Leptin modulates the angiogenic properties of hepatic stellate cells (HSC), but the molecular mechanisms involved are poorly understood. We investigated the pathways regulating hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) in leptin-stimulated myofibroblastic HSC. Exposure to leptin enhanced the phosphorylation of TSC2 on T1462 residues and of p70 S6 kinase and the translational inhibitor 4E-binding protein-1, indicating the ability of leptin to activate the mammalian target of rapamycin (mTOR) pathway. Similar findings were observed when HSC were exposed to PDGF. Both leptin and PDGF increased the expression of HIF-1α and VEGF in HSC. In the presence of rapamycin, a specific mTOR inhibitor, leptin and PDGF were no longer able to activate mTOR, and expression of VEGF was reduced, whereas HIF-1α abundance was not affected. Moreover, knockdown of Raptor, a component of the mTORC1 complex, reduced the ability of leptin to increase VEGF. mTOR was also necessary for leptin- and PDGF-dependent increase in HSC migration. Leptin increased the generation of reactive oxygen species in HSC, which was reduced by NADP(H) oxidase inhibitors. Both N-acetyl cysteine and diphenylene iodonium, a NADP(H) inhibitor, inhibited the expression of HIF-1α and VEGF stimulated by leptin or PDGF. Finally, conditioned media from HSC treated with leptin or PDGF induced tube formation in cultured human umbilical vein endothelial cells. In conclusion, in HSC exposed to leptin or PDGF, increased expression of VEGF requires both activation of mTOR and generation of reactive oxygen species via NADPH-oxidase. Induction of HIF-1α requires NADP(H) oxidase but not mTOR activation. 相似文献
999.
Stressful life events impact on memory, cognition and emotional responses, and are known to precipitate mood/anxiety disorders. It is increasingly recognized that stress and its neurochemical and endocrine mediators induce changes in glutamate synapses and circuitry, and this in turn modify mental states. Half a century after the monoamine hypothesis, it is widely accepted that maladaptive changes in excitatory/inhibitory circuitry have a primary role in the pathophysiology of mood/anxiety disorders. The neuroplasticity hypothesis posits that volumetric changes consistently found in limbic and cortical areas of depressed subjects are in good part due to remodeling of neuronal dendritic arbors and loss of synaptic spines. A considerable body of work, carried out with in vivo microdialysis as well as alternative methodologies, has shown that both stress and corticosterone treatment induce enhancement of activity-dependent glutamate release. Accordingly, results from preclinical studies suggest that stress- and glucocorticoid-induced enhancement of glutamate release and transmission plays a main role in the induction of maladaptive cellular effects, in turn responsible for dendritic remodeling.Additional recent work has showed that drugs employed for therapy of mood/anxiety disorders (antidepressants) prevent the enhancement of glutamate release induced by stress. Understanding the action of traditional drugs on glutamate transmission could be of great help in developing drugs that may work directly at this level. 相似文献
1000.
Brettanomyces/Dekkera yeasts have been identified as part of the grape yeast flora. They are well known for colonizing the cellar environmental and spoiling wines, causing haze, turbidity and strong off-flavours in wines and enhancing the volatile acidity. As the general practices applied to combat Brettanomyces/Dekkera yeasts are not particularly appropriate during wine ageing and storage, a biological alternative to curtailing their growth would be welcomed in winemaking. In this study, we investigated the Kluyveromyces wickerhamii killer toxin (Kwkt) that is active against Brettanomyces/Dekkera spoilage yeasts. Purification procedures allowed the identification of Kwkt as a protein with an apparent molecular mass of 72 kDa and without any glycosyl residue. Interestingly, purified Kwkt has fungicidal effects at low concentrations under the physicochemical conditions of winemaking. The addition of 40 and 80 mg L(-1) purified Kwkt showed efficient antispoilage effects, controlling both growth and metabolic activity of sensitive spoilage yeasts. At these two killer toxin concentrations, compounds known to contribute to the 'Brett' character of wines, such as ethyl phenols, were not produced. Thus, purified Kwkt appears to be a suitable biological strategy to control Brettanomyces/Dekkera yeasts during fermentation, wine ageing and storage. 相似文献