全文获取类型
收费全文 | 759篇 |
免费 | 51篇 |
国内免费 | 2篇 |
出版年
2022年 | 15篇 |
2021年 | 16篇 |
2020年 | 12篇 |
2019年 | 18篇 |
2018年 | 15篇 |
2017年 | 18篇 |
2016年 | 32篇 |
2015年 | 27篇 |
2014年 | 40篇 |
2013年 | 51篇 |
2012年 | 50篇 |
2011年 | 43篇 |
2010年 | 45篇 |
2009年 | 34篇 |
2008年 | 55篇 |
2007年 | 44篇 |
2006年 | 33篇 |
2005年 | 30篇 |
2004年 | 20篇 |
2003年 | 21篇 |
2002年 | 17篇 |
2001年 | 20篇 |
2000年 | 10篇 |
1999年 | 16篇 |
1998年 | 13篇 |
1997年 | 8篇 |
1996年 | 6篇 |
1995年 | 9篇 |
1994年 | 5篇 |
1993年 | 5篇 |
1992年 | 9篇 |
1991年 | 3篇 |
1990年 | 7篇 |
1989年 | 10篇 |
1988年 | 7篇 |
1987年 | 8篇 |
1986年 | 4篇 |
1985年 | 3篇 |
1984年 | 6篇 |
1983年 | 6篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1979年 | 2篇 |
1975年 | 1篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1970年 | 1篇 |
1969年 | 3篇 |
1965年 | 1篇 |
1964年 | 2篇 |
排序方式: 共有812条查询结果,搜索用时 211 毫秒
81.
A new synthetic strategy to get the PNA-3'DNA linker with the monomethoxytrityl (Mmt) group as temporary protection of the backbone to be used for the synthesis of PNA/DNA chimeras was employed and a convenient strategy to obtain Mmt PNA monomers was developed. The synthetic strategies take advantage of the introduction of the acid-labile Mmt-protecting group in the first step. 相似文献
82.
Brambilla M Manuguerra M Valente M Caramenti GC Sotgiu ML Biella GE 《Archives italiennes de biologie》2004,142(3):275-283
The Thalamo-Cortical somatosensory loop shows important synaptic re-organization in cases of chronic pain. Animal models exhibit severe functional distortions, potentially related to the anatomic rearrangements. Connectivity and information theoretic measurement represent important tools to quantify the functional disarrays. We performed electrophysiological experiments with multisite, multielectrode simultaneous recordings in the Thalamus and in the Somatosensory Cortex. The recurrent anomalies in the analytic estimates induce to hypothesize a potential neurodynamical explanation of the sensory context. 相似文献
83.
84.
M. Helena Garcia Andreia Valente Tânia S. Morais M. Teresa Duarte Francesc X. Avilés 《Inorganica chimica acta》2010,363(14):3765-3775
A new family of Ru(II) mixed metallocene complexes of the type [Ru(η5-C5H5)(η6-arene)][PF6] has been synthesized and fully characterized by NMR and UV-Vis spectroscopy. X-ray analysis of single crystal was achieved for all the complexes and revealed the presence of two enantiomers expected for planar chirality originated by the η6 coordination of the arene prochiral ligands. Studies of interaction of the new complexes with pBR322 DNA by atomic force microscopy showed very strong and different types of interaction. Antiproliferative tests were examined on human leukemia cancer cells (HL-60) using the MTT assay, and the IC50 values revealed low antiproliferative activity compared to cisplatin. 相似文献
85.
Venkatesan BA Mahimainathan L Ghosh-Choudhury N Gorin Y Bhandari B Valente AJ Abboud HE Choudhury GG 《Cellular signalling》2006,18(4):508-518
Monocyte chemotactic protein-1 (MCP-1) recruits activated phagocytes to the site of tissue injury. Interferon-gamma (IFN-gamma) present in the microenvironment of glomerulus acts on mesangial cells to induce local production of MCP-1. The mechanism by which IFN-gamma stimulates expression of MCP-1 is not clear. We therefore examined the role of PI 3 kinase signaling in regulating the IFN-gamma-induced MCP-1 expression in mesangial cells. Blocking PI 3 kinase activity with Ly294002 attenuated IFN-gamma-induced MCP-1 protein and mRNA expression. IFN-gamma increased Akt kinase activity in a PI 3 kinase-dependent manner. Expression of dominant negative Akt kinase inhibited serine phosphorylation of STAT1alpha, without any effect on its tyrosine phosphorylation, and decreased IFN-gamma-induced expression of MCP-1. These data for the first time indicate a role for PI 3 kinase-dependent Akt kinase in MCP-1 expression. We have recently shown that along with Akt, PKCepsilon is a downstream target of PI 3 kinase in IFN-gamma signaling. Similar to dominant negative Akt kinase, dominant negative PKCepsilon also inhibited serine phosphorylation of STAT1alpha without any effect on tyrosine phosphorylation. Dominant negative PKCepsilon also abrogated MAPK activity, resulting in decrease in IFN-gamma-induced MCP-1 expression. Furthermore, Akt and PKCepsilon are present together in a signaling complex. IFN-gamma had no effect on this complex formation, but did increase PKCepsilon-associated Akt kinase activity. PKCepsilon did not regulate IFN-gamma-induced Akt kinase. Finally, expression of dominant negative Akt kinase blocked IFN-gamma-stimulated MAPK activation. These data provide the first evidence that PI 3 kinase-dependent Akt and PKCepsilon activation independently regulate MAPK activity and serine phosphorylation of STAT1alpha to increase expression of MCP-1. 相似文献
86.
Patel DN Bailey SR Gresham JK Schuchman DB Shelhamer JH Goldstein BJ Foxwell BM Stemerman MB Maranchie JK Valente AJ Mummidi S Chandrasekar B 《Biochemical and biophysical research communications》2006,347(4):1113-1120
CXCL16 is a transmembrane non-ELR CXC chemokine that signals via CXCR6 to induce aortic smooth muscle cell (ASMC) proliferation. While bacterial lipopolysaccharide (LPS) has been shown to stimulate CXCL16 expression in SMC, its effects on CXCR6 are not known. Here, we demonstrate that LPS upregulates CXCR6 mRNA, protein, and surface expression in human ASMC. Inhibition of TLR4 with neutralizing antibodies or specific siRNA interference blocked LPS-mediated CXCR6 expression. LPS stimulated both AP-1 (c-Fos, c-Jun) and NF-kappaB (p50 and p65) activation, but only inhibition of AP-1 attenuated LPS-induced CXCR6 expression. Using dominant negative expression vectors and siRNA interference, we demonstrate that LPS induces AP-1 activation via MyD88, TRAF6, ERK1/2, and JNK signaling pathways. Furthermore, the flavoprotein inhibitor diphenyleniodonium chloride significantly attenuated LPS-mediated AP-1-dependent CXCR6 expression, as did inhibition of NOX4 NADPH oxidase by siRNA. Finally, CXCR6 knockdown inhibited CXCL16-induced ASMC proliferation. These results demonstrate that LPS-TLR4-NOX4-AP-1 signaling can induce CXCR6 expression in ASMC, and suggest that the CXCL16-CXCR6 axis may be an important proinflammatory pathway in the pathogenesis of atherosclerosis. 相似文献
87.
The Heteroduplex Mobility Assay (HMA) method using the PCR amplified D1/D2 region of the 26S rDNA was tested for the differentiation
of clinically relevant Candida species. Strains belonging to the same species are not expected to form heteroduplexes in this assay when their PCR products
are mixed. D1/D2 HMA experiments between all Candida type strains tested showed heteroduplex formation, including Candida albicans and Candida dubliniensis. There was no heteroduplex formation when most clinical and non-type strains were tested against the type strain of their
presumptive species, except when C. albicans WVE and C.␣dubliniensis TAI were analysed. Additional HMA experiments, phenotypic characterisation, and D1/D2 sequencing identified these isolates
as Candida tropicalis and Candida parapsilosis, respectively. HMA provides a rapid and relatively simple molecular tool for the differentiation of potentially pathogenic
Candida species. 相似文献
88.
89.
Pereira V Gusmão L Valente C Pereira R Carneiro J Gomes I Morling N Amorim A João Prata M 《American journal of physical anthropology》2012,148(3):389-394
Due to differences in transmission between X-chromosomal and autosomal DNA, the comparison of data derived from both markers allows deeper insight into the forces that shape the patterns of genetic diversity in populations. In this study, we applied this comparative approach to a sample of Portuguese Roma (Gypsies) by analyzing 43 X-chromosomal markers and 53 autosomal markers. Portuguese individuals of non-Gypsy ancestry were also studied. Compared with the host population, reduced levels of diversity on the X chromosome and autosomes were detected in Gypsies; this result was in line with known patterns of genetic diversity typical of Roma groups. As a consequence of the complex demographic past of the Roma, during which admixture and genetic drift played major roles, the amount of linkage disequilibrium (LD) on the X chromosome in Gypsies was considerably higher than that observed in non-Gypsies. When the pattern of differentiation on the X chromosome was compared with that of autosomes, there was evidence for asymmetries in female and male effective population sizes during the admixture between Roma and non-Roma. This result supplements previous data provided by mtDNA and the Y chromosome, underlining the importance of using combined information from the X chromosome and autosomes to dissect patterns of genetic diversity. Following the out-of-India dispersion, the Roma acquired a complex genetic pattern that was influenced by drift and introgression with surrounding populations, with important contributions from both males and females. We provide evidence that a sex-biased admixture with Europeans is probably associated with the founding of the Portuguese Gypsies. 相似文献
90.
Sergio Valente Ilaria Lepore Carmela Dell'Aversana Maria Tardugno Sabrina Castellano Gianluca Sbardella Stefano Tomassi Salvatore Di Maro Ettore Novellino Roberto Di Santo Roberta Costi Lucia Altucci Antonello Mai 《Biochimie》2012
Chemical manipulations undertaken on some bis(bromo- and dibromo-phenol) compounds previously reported by us as wide-spectrum epigenetic inhibitors let us to identify bis (bromo- and dibromo-methoxyphenyl) derivatives highly selective for PR-SET7 and EZH2 (compounds 4, 5, 9, and 10). Western blot analyses were carried out in U937 cells to determine the effects of such compounds on the methyl marks related to the tested enzymes (H3K4me1, H3K9me2, H4H20me1, and H3K27me3). The 1,5-bis(3-bromo-4-methoxyphenyl)penta-1,4-dien-3-one 4 (EC50 vs EZH2 = 74.9 μM), tested in U937 cells at 50 μM, induced massive cell death and 28% of granulocytic differentiation, highlighting the potential use of EZH2 inhibitors in cancer. 相似文献