全文获取类型
收费全文 | 1391篇 |
免费 | 97篇 |
专业分类
1488篇 |
出版年
2024年 | 4篇 |
2023年 | 16篇 |
2022年 | 22篇 |
2021年 | 54篇 |
2020年 | 27篇 |
2019年 | 35篇 |
2018年 | 40篇 |
2017年 | 27篇 |
2016年 | 39篇 |
2015年 | 83篇 |
2014年 | 72篇 |
2013年 | 103篇 |
2012年 | 120篇 |
2011年 | 122篇 |
2010年 | 70篇 |
2009年 | 80篇 |
2008年 | 96篇 |
2007年 | 77篇 |
2006年 | 75篇 |
2005年 | 61篇 |
2004年 | 51篇 |
2003年 | 44篇 |
2002年 | 39篇 |
2001年 | 15篇 |
2000年 | 9篇 |
1999年 | 13篇 |
1998年 | 10篇 |
1997年 | 14篇 |
1996年 | 3篇 |
1995年 | 6篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1991年 | 2篇 |
1990年 | 4篇 |
1989年 | 5篇 |
1988年 | 2篇 |
1987年 | 5篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1983年 | 4篇 |
1982年 | 4篇 |
1981年 | 2篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1975年 | 2篇 |
1973年 | 2篇 |
1969年 | 2篇 |
1967年 | 1篇 |
1962年 | 1篇 |
1960年 | 1篇 |
排序方式: 共有1488条查询结果,搜索用时 0 毫秒
11.
Israel Zilbermann Maya Winnik Dalia Sagiv Amira Rotman Haim Cohen Dan Meyerstein 《Inorganica chimica acta》1995,240(1-2):503-514
The effects of N-alkylation on the redox potential of the couples NiLi2+/NiLi+, L = tetraaza-14-membered-macrocyclic ligands, and on the properties of the monovalent nickel complexes in aqueous solutions are reported for 14 complexes. The spectra and lifetimes of the NiLi+ complexes are reported. The self-exchange rates for the couples NiLi2+/NiLi+ were determined. Two of the ligands were synthesized for the first time for this study. Cyclic voltammetry and pulse radiolysis were used. The results point out that: (i) N-alkylation always shifts the redox potential to a less cathodic one; this effect stems to a large degree from the decrease in the solvation energy of the complex caused by the N-alkylation of the ligand. (ii). The lifetime of the monovalent complexes is not linearly related to the redox potential of the NiLi2+/NiLi+ couples. (iii) The NiLi+ complexes exist in several isomeric forms; the rate of the isomerization depends on the structure of the ligand. (iv) Different isomers of NiLi+ may be formed when the complex NiLi2+ is reduced by different reagents; therefore, the pulse-radiolytically formed NiLi+ complexes might have different properties than those formed electrochemically. 相似文献
12.
13.
Chavan SS Huerta PT Robbiati S Valdes-Ferrer S Ochani M Dancho M Frankfurt M Volpe BT Tracey KJ Diamond B 《Molecular medicine (Cambridge, Mass.)》2012,18(9):930-937
Severe sepsis, a syndrome that complicates infection and injury, affects 750,000 annually in the United States. The acute mortality rate is approximately 30%, but, strikingly, sepsis survivors have a significant disability burden: up to 25% of survivors are cognitively and physically impaired. To investigate the mechanisms underlying persistent cognitive impairment in sepsis survivors, here we developed a murine model of severe sepsis survivors following cecal ligation and puncture (CLP) to study cognitive impairments. We observed that serum levels of high mobility group box 1 (HMGB1), a critical mediator of acute sepsis pathophysiology, are increased in sepsis survivors. Significantly, these levels remain elevated for at least 4 wks after CLP. Sepsis survivors develop significant, persistent impairments in learning and memory, and anatomic changes in the hippocampus associated with a loss of synaptic plasticity. Administration of neutralizing anti-HMGB1 antibody to survivors, beginning 1 wk after onset of peritonitis, significantly improved memory impairments and brain pathology. Administration of recombinant HMGB1 to na?ve mice recapitulated the memory impairments. Together, these findings indicate that elevated HMGB1 levels mediate cognitive decline in sepsis survivors, and suggest that it may be possible to prevent or reverse cognitive impairments in sepsis survivors by administration of anti-HMGB1 antibodies. 相似文献
14.
Gruber Véronique Berna Patrick P. Arnaud Thierry Bournat Philippe Clément Christèle Mison Dominique Olagnier Béatrice Philippe Laurence Theisen Manfred Baudino Sylvie Bénicourt Claude Cudrey Claire Bloës Carole Duchateau Nathalie Dufour Sylvie Gueguen Catherine Jacquet Séverine Ollivo Catherine Poncetta Christine Zorn Nathalie Ludevid Dolores Van Dorsselaer Alain Verger Robert Doherty Annette Mérot Bertrand Danzin Charles 《Molecular breeding : new strategies in plant improvement》2001,7(4):329-340
A recombinant dog gastric lipase with therapeutic potential for the treatment of exocrine pancreatic insufficiency was expressed in transgenic tobacco plants. We targeted the protein using two different signal sequences for either vacuolar retention or secretion. In both cases, an active glycosylated recombinant protein was obtained. The recombinant enzymes and the native enzyme displayed similar properties including acid resistance and acidic optimum pH. The proteolytic maturation and the specific activity of the recombinant proteins, however, were found to be dependent on subcellular compartmentalization. Expression levels of recombinant dog gastric lipase were about 5% and 7% of acid extractable plant proteins for vacuolar retention and secretion respectively. This expression system already has allowed the production of tens of grams of purified lipase through open-field culture of transgenic tobacco plants. 相似文献
15.
16.
Ana Bortolotti Ana Sánchez-Azqueta Celia M. Maya Adrián Velázquez-Campoy Juan A. Hermoso Milagros Medina Néstor Cortez 《BBA》2014
To study the role of the mobile C-terminal extension present in bacterial class of plant type NADP(H):ferredoxin reductases during catalysis, we generated a series of mutants of the Rhodobacter capsulatus enzyme (RcFPR). Deletion of the six C-terminal amino acids beyond alanine 266 was combined with the replacement A266Y, emulating the structure present in plastidic versions of this flavoenzyme. Analysis of absorbance and fluorescence spectra suggests that deletion does not modify the general geometry of FAD itself, but increases exposure of the flavin to the solvent, prevents a productive geometry of FAD:NADP(H) complex and decreases the protein thermal stability. Although the replacement A266Y partially coats the isoalloxazine from solvent and slightly restores protein stability, this single change does not allow formation of active charge-transfer complexes commonly present in the wild-type FPR, probably due to restraints of C-terminus pliability. A proton exchange process is deduced from ITC measurements during coenzyme binding. All studied RcFPR variants display higher affinity for NADP+ than wild-type, evidencing the contribution of the C-terminus in tempering a non-productive strong (rigid) interaction with the coenzyme. The decreased catalytic rate parameters confirm that the hydride transfer from NADPH to the flavin ring is considerably hampered in the mutants. Although the involvement of the C-terminal extension from bacterial FPRs in stabilizing overall folding and bent-FAD geometry has been stated, the most relevant contributions to catalysis are modulation of coenzyme entrance and affinity, promotion of the optimal geometry of an active complex and supply of a proton acceptor acting during coenzyme binding. 相似文献
17.
Sok‐Keng Tong Karen Mouriec Ming‐Wei Kuo Elisabeth Pellegrini Marie‐Madeleine Gueguen François Brion Olivier Kah Bon‐chu Chung 《Genesis (New York, N.Y. : 2000)》2009,47(2):67-73
Aromatase is an enzyme that catalyzes the synthesis of estrogen in gonads and brain. Teleost fish express aromatase (AroB) strongly in the brain facilitating its detailed examination. To understand the function of AroB in the brain, we generated transgenic zebrafish that expresses green fluorescent protein (GFP) driven by the brain aromatase cyp19a1b promoter. GFP was found in the radial glial cells of transgenic larvae and adult fish that overlap with AroB immunoreactivity in the correct temporal and spatial pattern. GFP was also coexpressed with radial cell marker BLBP, but was not in neurons. In addition, GFP expression in the radial glial cells was stimulated by estrogen, same as endogenous AroB expression. Thus, this transgenic line faithfully mimics the regulation of AroB expression in radial glial cells. It provides a powerful tool to further characterize progenitor radial cells in adult and developing fish and to evaluate estrogenic activities of xenoestrogens and phytoestrogens. genesis 47:67–73, 2009. © 2008 Wiley‐Liss, Inc. 相似文献
18.
Exercise is an effective approach for primary and secondary prevention of cardiovascular diseases (CVD) and loss of muscular mass and function. Its benefits are widely documented but incompletely characterized. It has been reported that exercise can induce changes in the expression of antioxidant enzymes including Sod2, Trx1, Prdx3 and Gpx1 and limits the rise in oxidative stress commonly associated with CVD. These enzymes can be subjected to epigenetic regulation, such as DNA methylation, in response to environmental cues. The aim of our study was to determine whether in the early stages of atherogenesis, in young severely dyslipidemic mice lacking LDL receptors and overexpressing human ApoB100 (LDLR-/-; hApoB+/+), exercise regulates differentially the expression of antioxidant enzymes by DNA methylation in the skeletal muscles that consume high levels of oxygen and thus generate high levels of reactive oxygen species. Expression of Sod2, Txr1, Prdx3 and Gpx1 was altered by 3 months of exercise and/or severe dyslipidemia in 6-mo dyslipidemic mice. Of these genes, only Gpx1 exhibited changes in DNA methylation associated with dyslipidemia and exercise: we observed both increased DNA methylation with dyslipidemia and a transient decrease in DNA methylation with exercise. These epigenetic alterations are found in the second exon of the Gpx1 gene and occur alongside with inverse changes in mRNA expression. Inhibition of expression by methylation of this specific locus was confirmed in vitro. In conclusion, Gpx1 expression in the mouse skeletal muscle can be altered by both exercise and dyslipidemia through changes in DNA methylation, leading to a fine regulation of free radical metabolism. 相似文献
19.
Maya Shirakura Hidetaka Eguchi Hideaki Nakamura Keiko Hiyama Eiji Tanaka Takashi Takata 《Biochemical and biophysical research communications》2010,393(4):800-805
Vascular endothelial growth factor (Vegf) was previously shown to be expressed specifically in the condylar cartilage of temporomandibular joint-osteoarthritis (TMJ-OA) model rats. Here we demonstrate for the first time that hypoxia-inducible factor-1α (Hif-1α) is activated in mature chondrocytes of temporomandibular joint-osteoarthritis (TMJ-OA) model rat by mechanical overload, and that activated Hif-1 in chondrocytes can induce osteoclastogenesis via repression of osteoprotegerin (Opg) expression.In rat TMJs, degeneration of the condylar cartilage became prominent in proportion to the duration of overloading. Hif-1α expression was observed specifically in mature and hypertrophic chondrocytes, and Hif-1α-positivity, level of Vegf expression, and tartrate-resistant acid phosphatase (TRAP)-positive cell numbers all increased in the same manner. When ATDC5 cells induced differentiation by insulin were cultured under hypoxia, Hif-1α induction was observed in mature stage, but not in immature stage. Inductions of Hif-1-target genes showed a similar expression pattern. In addition, expression of Opg decreased in hypoxia, and Hif-1α played a role, in part, in its regulation. 相似文献
20.
Epithelial cells isolated from rat lung and trachea were grown on monolayers and their response to a number of hormones and
growth factors were studied. Maximum proliferative response in serum containing media was observed when insulin, cholera toxin
and cortisol were present together. However, these additives when present independently showed a marginal response. The synergism,
due to these factors in promoting growth was seen very early in culture (day 4) as shown by thymidine labelling studies, On
examining the indices of early mitogenesis, such as the expression ofc-myc, our data suggests that these factors stimulate the expression ofc-myc within 4 h. With respect to expression of TNF-α mRNA, this study suggests a possible modulation of TNF-α expression in response
to these mitogens that stimulate proliferation maximally. Whether this expression of TNF-α by these epithelial cells is due
to a maximal proliferative stimulus and/or is an early step in the cascade of intracellular signalling events is to be investigated
in detail. 相似文献