全文获取类型
收费全文 | 611篇 |
免费 | 38篇 |
出版年
2023年 | 5篇 |
2022年 | 6篇 |
2021年 | 20篇 |
2020年 | 14篇 |
2019年 | 16篇 |
2018年 | 18篇 |
2017年 | 11篇 |
2016年 | 19篇 |
2015年 | 31篇 |
2014年 | 39篇 |
2013年 | 43篇 |
2012年 | 59篇 |
2011年 | 45篇 |
2010年 | 28篇 |
2009年 | 19篇 |
2008年 | 26篇 |
2007年 | 41篇 |
2006年 | 30篇 |
2005年 | 31篇 |
2004年 | 31篇 |
2003年 | 19篇 |
2002年 | 17篇 |
2001年 | 4篇 |
2000年 | 5篇 |
1999年 | 4篇 |
1998年 | 11篇 |
1997年 | 3篇 |
1996年 | 1篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 4篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1981年 | 2篇 |
1980年 | 3篇 |
1978年 | 4篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1970年 | 4篇 |
排序方式: 共有649条查询结果,搜索用时 15 毫秒
61.
62.
Braeuning A Singh Y Rignall B Buchmann A Hammad S Othman A von Recklinghausen I Godoy P Hoehme S Drasdo D Hengstler JG Schwarz M 《Histochemistry and cell biology》2010,134(5):469-481
Signaling through the Wnt/β-catenin pathway is a crucial determinant of hepatic zonal gene expression, liver development, regeneration, and tumorigenesis. Transgenic mice with hepatocyte-specific knockout of Ctnnb1 (encoding β-catenin) have proven their usefulness in elucidating these processes. We now found that a small number of hepatocytes escape the Cre-mediated gene knockout in that mouse model. The remaining β-catenin-positive hepatocytes showed approximately 25% higher cell volumes compared to the β-catenin-negative cells and exhibited a marker protein expression profile similar to that of normal perivenous hepatocytes or hepatoma cells with mutationally activated β-catenin. Surprisingly, the expression pattern was observed independent of the cell's position within the liver lobule, suggesting a malfunction of physiological periportal repression of perivenously expressed genes in β-catenin-deficient liver. Clusters of β-catenin-expressing hepatocytes lacked expression of the gap junction proteins Connexin 26 and 32. Nonetheless, β-catenin-positive hepatocytes had no striking proliferative advantage, but started to grow out on treatment with phenobarbital, a tumor-promoting agent known to facilitate the formation of mouse liver adenoma with activating mutations of Ctnnb1. Progressive re-population of Ctnnb1 knockout livers with wild-type hepatocytes was seen in aged mice with a pre-cirrhotic phenotype. In these large clusters of β-catenin-expressing hepatocytes, perivenous-specific gene expression was re-established. In summary, our data demonstrate that the zone-specificity of a hepatocyte's gene expression profile is dependent on the presence of β-catenin, and that β-catenin provides a proliferative advantage to hepatocytes when promoted with phenobarbital, or in a pre-cirrhotic environment. 相似文献
63.
Patricio Villalobos Cristian A. Acevedo Fernando Albornoz Elizabeth Sánchez Erika Valdés Raúl Galindo Manuel E. Young 《Bioprocess and biosystems engineering》2010,33(8):961-970
Biochemical oxygen demand (BOD) is a measure of the amount of dissolved oxygen that is required for the biochemical oxidation
of the organic compounds in 5 days. New biosensor-based methods have been conducted for a faster determination of BOD. In
this study, a mathematical model to evaluate the feasibility of using a BOD sensor, based on disposable alginate-entrapped
bacteria, for monitoring BOD in situ was applied. The model considers the influences of alginate bead size and bacterial concentration.
The disposable biosensor can be adapted according to specific requirements depending on the organic load contained in the
wastewater. Using Klein and Washausen parameter in a Lineweaver–Burk plot, the glucose diffusivity was calculated in 6.4 × 10−10 (m2/s) for beads of 1 mm in diameter and slight diffusion restrictions were observed (n = 0.85). Experimental results showed a correlation (p < 0.05) between the respirometric peak and the standard BOD test. The biosensor response was representative of BOD. 相似文献
64.
López PG Tremetsberger K Stuessy TF Gómez-González S Jiménez A Baeza CM 《American journal of botany》2010,97(3):423-432
The effect of colonization on the distribution of genetic diversity within and among populations in relation to species characteristics remains an open empirical question. The objective of this study was to contrast genetic diversity within and among established and colonizing populations of Nassauvia lagascae var. lanata on Volcán Lonquimay (Araucanía Region, Chile), which erupted on 25 December 1988, and relate genetic diversity to biological characteristics of the populations. We analyzed a total of 240 individuals from 15 populations distributed along the Andes Cordillera using AFLP and obtained a total of 307 AFLP bands, of which 97.7% are polymorphic. Values of population differentiation (F(ST)) did not differ significantly among established and colonizing populations, but colonizing populations did have reduced levels of genetic divergence (as indicated by private and rare bands) and genetic variation (e.g., Shannon index). We conclude that a founder effect through limited numbers of founding propagules derived from nearby source populations has not yet been compensated for by subsequent population growth and migration. Low rates of secondary dispersal via running water, kin-structure within populations, and slow population growth seem to contribute to the slow recovery of genetic diversity. 相似文献
65.
Quiroga AG Cubo L de Blas E Aller P Navarro-Ranninger C 《Journal of inorganic biochemistry》2007,101(1):104-110
In an attempt to design new antitumoral drugs based on transplatin complexes, we determined the experimental conditions for the preparation of trans-[Pt((CH(3))(2)CNOH)((CH(3))(2)CHNH(2))Cl(2)], and solved the crystal structure. The cytotoxicity of the novel complex, the cis counterpart, cisplatin, and a trans complex with aliphatic amines, as well as the capacity of some of these complexes to cause either apoptotic or necrotic cell death, was comparatively examined in NRK-52E rat renal tubular cells and HepG2 human hepatoma cells. The results indicate that the oxime complex with trans geometry, but not the one with cis geometry, causes death by apoptosis, making the complex potentially suitable for therapeutic purposes. However cytotoxicity values are higher in the case of cis geometry than in trans geometry in both tumoral and non-tumoral cell lines. 相似文献
66.
67.
68.
Fuenzalida K Quintanilla R Ramos P Piderit D Fuentealba RA Martinez G Inestrosa NC Bronfman M 《The Journal of biological chemistry》2007,282(51):37006-37015
Peroxisome proliferator-activated receptor gamma (PPARgamma) has been proposed as a therapeutic target for neurodegenerative diseases because of its anti-inflammatory action in glial cells. However, PPARgamma agonists preventbeta-amyloid (Abeta)-induced neurodegeneration in hippocampal neurons, and PPARgamma is activated by the nerve growth factor (NGF) survival pathway, suggesting a neuroprotective anti-inflammatory independent action. Here we show that the PPARgamma agonist rosiglitazone (RGZ) protects hippocampal and dorsal root ganglion neurons against Abeta-induced mitochondrial damage and NGF deprivation-induced apoptosis, respectively, and promotes PC12 cell survival. In neurons and in PC12 cells RGZ protective effects are associated with increased expression of the Bcl-2 anti-apoptotic protein. NGF-differentiated PC12 neuronal cells constitutively overexpressing PPARgamma are resistant to Abeta-induced apoptosis and morphological changes and show functionally intact mitochondria and no increase in reactive oxygen species when challenged with up to 50 microM H2O2. Conversely, cells expressing a dominant negative mutant of PPARgamma show increased Abeta-induced apoptosis and disruption of neuronal-like morphology and are highly sensitive to oxidative stress-induced impairment of mitochondrial function. Cells overexpressing PPARgamma present a 4- to 5-fold increase in Bcl-2 protein content, whereas in dominant negative PPARgamma-expressing cells, Bcl-2 is barely detected. Bcl-2 knockdown by small interfering RNA in cells overexpressing PPARgamma results in increased sensitivity to Abeta and oxidative stress, further suggesting that Bcl-2 up-regulation mediates PPARgamma protective effects. PPARgamma prosurvival action is independent of the signal-regulated MAPK or the Akt prosurvival pathways. Altogether, these data suggest that PPARgamma supports survival in neurons in part through a mechanism involving increased expression of Bcl-2. 相似文献
69.
70.