全文获取类型
收费全文 | 688篇 |
免费 | 68篇 |
出版年
2022年 | 9篇 |
2021年 | 8篇 |
2020年 | 4篇 |
2019年 | 10篇 |
2018年 | 17篇 |
2017年 | 16篇 |
2016年 | 17篇 |
2015年 | 25篇 |
2014年 | 36篇 |
2013年 | 45篇 |
2012年 | 41篇 |
2011年 | 49篇 |
2010年 | 34篇 |
2009年 | 20篇 |
2008年 | 43篇 |
2007年 | 28篇 |
2006年 | 31篇 |
2005年 | 25篇 |
2004年 | 21篇 |
2003年 | 23篇 |
2002年 | 22篇 |
2001年 | 21篇 |
2000年 | 20篇 |
1999年 | 16篇 |
1998年 | 12篇 |
1997年 | 10篇 |
1996年 | 9篇 |
1995年 | 6篇 |
1994年 | 5篇 |
1993年 | 4篇 |
1992年 | 10篇 |
1991年 | 6篇 |
1990年 | 9篇 |
1989年 | 10篇 |
1987年 | 3篇 |
1986年 | 11篇 |
1984年 | 10篇 |
1983年 | 4篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1978年 | 4篇 |
1976年 | 3篇 |
1974年 | 4篇 |
1973年 | 4篇 |
1972年 | 3篇 |
1971年 | 3篇 |
1969年 | 3篇 |
1968年 | 4篇 |
1939年 | 6篇 |
1938年 | 11篇 |
排序方式: 共有756条查询结果,搜索用时 15 毫秒
31.
Alexander Bürkle Graziella Caselli Claudio Franceschi Erminia Mariani Paolo Sansoni Angela Santoni Giancarlo Vecchio Jacek M Witkowski Calogero Caruso 《Immunity & ageing : I & A》2007,4(1):4-8
On April 18, 2007 an international meeting on Pathophysiology of Ageing, Longevity and Age-Related Diseases was held in Palermo,
Italy. Several interesting topics on Cancer, Immunosenescence, Age-related inflammatory diseases and longevity were discussed.
In this report we summarize the most important issues. However, ageing must be considered an unavoidable end point of the
life history of each individual, nevertheless the increasing knowledge on ageing mechanisms, allows envisaging many different
strategies to cope with, and delay it. So, a better understanding of pathophysiology of ageing and age-related disease is
essential for giving everybody a reasonable chance for living a long and enjoyable final part of the life. 相似文献
32.
Jung H. Y. Park Mark R. Corkins Jon A. Vanderhoof Nia M. Caruso Marjorie J. Hrbek Beverly S. Schaffer Dorothy H. Slentz Robert H. McCusker Richard G. MacDonald 《Journal of cellular physiology》1996,166(2):396-406
The components of the insulin-like growth factor (IGF) axis and their roles in regulating proliferation and differentiation of the human colon adenocarcinoma cell line, Caco-2, have been investigated. Caco-2 cells proliferated in serum-free medium at 75% the rate observed in medium containing 10% fetal bovine serum. IGF-I (10 nM) increased Caco-2 cell growth in serum-free medium, but not to the rate seen with serum. Multiple IGF-II mRNA species were produced by Caco-2 cells, but IGF-I mRNA was undetectable. Secretion of radioimmunoassayable IGF-II corresponded with steady-state levels of IGF-II mRNA, neither of which was observed to change markedly over the course of 16 days of Caco-2 cell differentiation. Levels of sucrase-isomaltase mRNA, a marker for enterocytic differentiation, increased 12-fold between days 5 and 16 of culture. Northern blotting of total RNA and ligand blot and immunoblot analyses of serum-free conditioned medium revealed that Caco-2 cells produce several IGF binding proteins (IGFBPs), including IGFBP-2, -3, and -4, as well as a 31,000 M, species that was not identified. The pattern of IGFBP secretion changed dramatically during Caco-2 cell differentiation: IGFBP-3 and IGFBP-2 increased 8.5-fold and 5-fold, respectively, whereas IGFBP-4 and the 31,000 M, species decreased 43% and 90%. Caco-2 cell clones stably transfected with a human IGFBP-4 cDNA construct exhibited a 60% increase in steady-state level of IGFBP-4 mRNA, and secreted twice as much IGFBP-4 protein as controls. Moreover, IGFBP-4-overexpressing cells proliferated at only 25% the rate of control cells in serum-free medium, in conjunction with a 70% increase in expression of sucrase-isomaltase. In summary, these studies indicate that a complex IGF axis is involved in autocrine regulation of Caco-2 cell proliferation and differentiation. © 1996 Wiley-Liss, Inc. 相似文献
33.
Sahar Keshvari Berit Genz Ngari Teakle Melanie Caruso Michelle F. Cestari Omkar L. Patkar Brian W. C. Tse Kamil A. Sokolowski Hilmar Ebersbach Julia Jascur Kelli P. A. MacDonald Gregory Miller Grant A. Ramm Allison R. Pettit Andrew D. Clouston Elizabeth E. Powell David A. Hume Katharine M. Irvine 《Disease models & mechanisms》2022,15(4)
34.
Caruso M Maitan MA Bifulco G Miele C Vigliotta G Oriente F Formisano P Beguinot F 《The Journal of biological chemistry》2001,276(48):45088-45097
In L6 skeletal muscle cells and immortalized hepatocytes, insulin induced a 2-fold increase in the activity of the pyruvate dehydrogenase (PDH) complex. This effect was almost completely blocked by the protein kinase C (PKC) delta inhibitor Rottlerin and by PKCdelta antisense oligonucleotides. At variance, overexpression of wild-type PKCdelta or of an active PKCdelta mutant induced PDH complex activity in both L6 and liver cells. Insulin stimulation of the activity of the PDH complex was accompanied by a 2.5-fold increase in PDH phosphatases 1 and 2 (PDP1/2) activity with no change in the activity of PDH kinase. PKCdelta antisense blocked insulin activation of PDP1/2, the same as with PDH. In insulin-exposed cells, PDP1/2 activation was paralleled by activation and mitochondrial translocation of PKCdelta, as revealed by cell subfractionation and confocal microscopy studies. The mitochondrial translocation of PKCdelta, like its activation, was prevented by Rottlerin. In extracts from insulin-stimulated cells, PKCdelta co-precipitated with PDP1/2. PKCdelta also bound to PDP1/2 in overlay blots, suggesting that direct PKCdelta-PDP interaction may occur in vivo as well. In intact cells, insulin exposure determined PDP1/2 phosphorylation, which was specifically prevented by PKCdelta antisense. PKCdelta also phosphorylated PDP in vitro, followed by PDP1/2 activation. Thus, in muscle and liver cells, insulin causes activation and mitochondrial translocation of PKCdelta, accompanied by PDP phosphorylation and activation. These events are necessary for insulin activation of the PDH complex in these cells. 相似文献
35.
Klein RC Siarey RJ Caruso A Rapoport SI Castellino FJ Galdzicki Z 《Journal of neurochemistry》2001,76(6):1663-1669
The trisomy 16 (Ts16) mouse is an animal model for human trisomy 21 (Down's syndrome). The gene encoding the NR2A subunit of the NMDA receptor has been localized to mouse chromosome 16. In the present study, western blot analysis revealed a 2.5-fold increase of NR2A expression in cultured Ts16 embryonic hippocampal neurons. However, this increase did not affect the properties of NMDA-evoked currents in response to various modulators. The sensitivity of NMDA receptors to transient applications of NMDA, spermine, and Zn(2+) was investigated in murine Ts16 and control diploid cultured embryonic hippocampal neurons. Peak and steady-state currents evoked by NMDA were potentiated by spermine at concentrations < 1 mM, and inhibited by Zn(2+) in a dose-dependent and voltage-independent manner. No marked difference was observed between Ts16 and control diploid neurons for any of these modulators with regard to IC(50) and EC(50) values or voltage dependency. Additionally, inhibition by the NR2B selective inhibitor, ifenprodil, was similar. These results demonstrate that NMDA-evoked currents are not altered in cultured embryonic Ts16 neurons and suggest that Ts16 neurons contain similar functional properties of NMDA receptors as diploid control neurons despite an increased level of NR2A expression. 相似文献
36.
Clementi G Caruso A Cutuli VM Prato A Mangano NG Amico-Roxas M 《Life sciences》1999,65(15):PL203-PL208
The antiinflammatory effect of ADM was studied in different models of inflammation and compared to the one of CGRP. Peptides were active against acetic acid-induced peritonitis in the rats. ADM and CGRP exerted the antiinflammatory effect at different doses, 400 and 20 ng/kg respectively, but with different efficacy (ADM >CGRP). This effect was blocked by pretreatment with CGRP (8-37) fragment or with L-NAME. No antiinflammatory activity was evidenced against serotonin- or carrageenin-induced rat paw edema. Our data suggest that ADM exerts antiinflammatory activity in the model characterized by a vascular component. This effect involves CGRP receptors and appears to be mediated by nitric oxide system. 相似文献
37.
Overexpression of selenocysteine methyltransferase in Arabidopsis and Indian mustard increases selenium tolerance and accumulation 总被引:11,自引:0,他引:11
LeDuc DL Tarun AS Montes-Bayon M Meija J Malit MF Wu CP AbdelSamie M Chiang CY Tagmount A deSouza M Neuhierl B Böck A Caruso J Terry N 《Plant physiology》2004,135(1):377-383
A major goal of phytoremediation is to transform fast-growing plants with genes from plant species that hyperaccumulate toxic trace elements. We overexpressed the gene encoding selenocysteine methyltransferase (SMT) from the selenium (Se) hyperaccumulator Astragalus bisulcatus in Arabidopsis and Indian mustard (Brassica juncea). SMT detoxifies selenocysteine by methylating it to methylselenocysteine, a nonprotein amino acid, thereby diminishing the toxic misincorporation of Se into protein. Our Indian mustard transgenic plants accumulated more Se in the form of methylselenocysteine than the wild type. SMT transgenic seedlings tolerated Se, particularly selenite, significantly better than the wild type, producing 3- to 7-fold greater biomass and 3-fold longer root lengths. Moreover, SMT plants had significantly increased Se accumulation and volatilization. This is the first study, to our knowledge, in which a fast-growing plant was genetically engineered to overexpress a gene from a hyperaccumulator in order to increase phytoremediation potential. 相似文献
38.
Amari G Armani E Ghirardi S Delcanale M Civelli M Caruso PL Galbiati E Lipreri M Rivara S Lodola A Mor M 《Bioorganic & medicinal chemistry》2004,12(14):3763-3782
The synthesis, binding affinity for estrogen receptor subtypes (ER alpha and ER beta) and pharmacological activity on rat uterus of a new class of potent ligands, characterized by a 3-phenylbenzopyran scaffold with a basic side chain in position 4, are reported. Some of these compounds, endowed with very high receptor affinity, showed potent inhibition of agonist-stimulated uterine growth, with no or limited proliferative effect. Binding affinity mostly depended on the nature and position of substituents at the 3-phenyl ring, while the uterine activity seems to be affected by basic chain length. Compound 9c (CHF4227) showed excellent binding affinity and antagonist activity on the uterus. The docking of benzopyran derivatives explained the structure-affinity relationships observed for 3-phenyl substitution: a small, hydrophobic 4'-substituent could interact with a small accessory binding cavity, while di-substitution at 4' and 3' led to some ER alpha selectivity. This selectivity can be ascribed to differences in amino acid composition and side chain conformation in the region accommodating the 3-phenyl ring at human ER alpha and ER beta ligand-binding domain. 相似文献
39.
40.
The strength and direction of natural selection on floral traits can vary spatially and temporally because of variation in the biotic and abiotic environment. High spatial variation in selection should lead to differentiation of floral traits among populations. In contrast, high temporal variation in selection should retard the evolution of population-specific floral phenotypes. To determine the relative importance of spatial vs. temporal variation in natural selection, we measured phenotypic selection on seven floral traits of the wildflowers Lobelia cardinalis and L. siphilitica in 1999 and 2000. Lobelia cardinalis experienced significant temporal variation in selection, whereas L. siphilitica experienced spatial variation in selection on the same traits. This variation in selection on floral traits was associated with spatial and temporal differences in the soil microenvironment. Although few studies of natural selection include spatial or temporal replicates, our results suggest that such replication is critical for understanding the distribution of phenotypes in nature. 相似文献