全文获取类型
收费全文 | 214篇 |
免费 | 9篇 |
出版年
2019年 | 1篇 |
2018年 | 1篇 |
2017年 | 1篇 |
2016年 | 2篇 |
2015年 | 7篇 |
2014年 | 9篇 |
2013年 | 10篇 |
2012年 | 16篇 |
2011年 | 10篇 |
2010年 | 14篇 |
2009年 | 7篇 |
2008年 | 9篇 |
2007年 | 12篇 |
2006年 | 11篇 |
2005年 | 13篇 |
2004年 | 5篇 |
2003年 | 6篇 |
2002年 | 7篇 |
2001年 | 5篇 |
2000年 | 8篇 |
1999年 | 5篇 |
1998年 | 5篇 |
1997年 | 2篇 |
1996年 | 4篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 4篇 |
1987年 | 5篇 |
1986年 | 2篇 |
1985年 | 4篇 |
1984年 | 4篇 |
1983年 | 1篇 |
1980年 | 3篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1973年 | 2篇 |
1971年 | 2篇 |
1970年 | 2篇 |
1968年 | 1篇 |
1965年 | 1篇 |
1963年 | 1篇 |
1962年 | 1篇 |
1957年 | 1篇 |
排序方式: 共有223条查询结果,搜索用时 875 毫秒
121.
Liu XP Goldring CE Copple IM Wang HY Wei W Kitteringham NR Park BK 《Life sciences》2007,80(17):1586-1591
The standard extract of Ginkgo biloba (EGb) has been demonstrated to possess remarkable antioxidant activity in both cell lines and animals. However, the molecular mechanism underlying this effect is not fully understood. Phase 2 enzymes play important roles in the antioxidant system by reducing electrophiles and reactive oxygen species (ROS). We demonstrated that EGb induced typical phase 2 genes: glutamate cysteine ligase catalytic subunit (GCLC) and glutathione-S-transferase subunit-P1 (GST-P1), by real-time PCR. To investigate the molecular mechanism of this induction, we used quinone oxidoreductase 1 (NQO1) -- Antioxidant response element (ARE) reporter assay and found that EGb activated the activity of the wild type but not the one with ARE mutated. It indicated that EGb induced these genes through ARE, a cis-acting motif located in the promoter region of nearly all phase 2 genes. Since nuclear factor erythroid 2-related factor 2 (Nrf2) binds ARE to enhance the expression of phase 2 genes, we detected the Nrf2 content in nucleus and found an accumulation of Nrf2 stimulated by EGb. In a further test of Kelch-like ECH-associated protein 1 (Keap1), the repression protein of Nrf2 in the cytosol under resting condition, we found that Keap1 content was inhibited by EGb and then more Nrf2 would be released to translocate into nucleus. Thus, EGb was testified for the first time to induce the phase 2 genes through the Keap1-Nrf2-ARE signaling pathway, which is (or part of) the antioxidant mechanism of EGb. 相似文献
122.
Fortunato Ferrara Sara D’Angelo Tiziano Gaiotto Leslie Naranjo Hongzhao Tian Susanne Gr?slund Elena Dobrovetsky Peter Hraber Fridtjof Lund-Johansen Silvia Saragozza Daniele Sblattero Csaba Kiss Andrew RM Bradbury 《MABS-AUSTIN》2015,7(1):32-41
Only a small fraction of the antibodies in a traditional polyclonal antibody mixture recognize the target of interest, frequently resulting in undesirable polyreactivity. Here, we show that high-quality recombinant polyclonals, in which hundreds of different antibodies are all directed toward a target of interest, can be easily generated in vitro by combining phage and yeast display. We show that, unlike traditional polyclonals, which are limited resources, recombinant polyclonal antibodies can be amplified over one hundred million-fold without losing representation or functionality. Our protocol was tested on 9 different targets to demonstrate how the strategy allows the selective amplification of antibodies directed toward desirable target specific epitopes, such as those found in one protein but not a closely related one, and the elimination of antibodies recognizing common epitopes, without significant loss of diversity. These recombinant renewable polyclonal antibodies are usable in different assays, and can be generated in high throughput. This approach could potentially be used to develop highly specific recombinant renewable antibodies against all human gene products. 相似文献
123.
124.
Lúcia de Paula Célio L Silva Daniela Carlos Camila Matias-Peres Carlos A Sorgi Edson G Soares Patrícia RM Souza Carlos RZ Bladés Fábio CS Galleti Vânia LD Bonato Eduardo DC Gonçalves Érika VG Silva Lúcia H Faccioli 《Genetic vaccines and therapy》2007,5(1):1-7
The great challenges for researchers working in the field of vaccinology are optimizing DNA vaccines for use in humans or large animals and creating effective single-dose vaccines using appropriated controlled delivery systems. Plasmid DNA encoding the heat-shock protein 65 (hsp65) (DNAhsp65) has been shown to induce protective and therapeutic immune responses in a murine model of tuberculosis (TB). Despite the success of naked DNAhsp65-based vaccine to protect mice against TB, it requires multiple doses of high amounts of DNA for effective immunization. In order to optimize this DNA vaccine and simplify the vaccination schedule, we coencapsulated DNAhsp65 and the adjuvant trehalose dimycolate (TDM) into biodegradable poly (DL-lactide-co-glycolide) (PLGA) microspheres for a single dose administration. Moreover, a single-shot prime-boost vaccine formulation based on a mixture of two different PLGA microspheres, presenting faster and slower release of, respectively, DNAhsp65 and the recombinant hsp65 protein was also developed. These formulations were tested in mice as well as in guinea pigs by comparison with the efficacy and toxicity induced by the naked DNA preparation or BCG. The single-shot prime-boost formulation clearly presented good efficacy and diminished lung pathology in both mice and guinea pigs. 相似文献
125.
Shen Z Crotti TN Flannery MR Matsuzaki K Goldring SR McHugh KP 《Biochimica et biophysica acta》2007,1769(11-12):659-667
126.
127.
128.
The control of chondrogenesis 总被引:19,自引:0,他引:19
129.
Marta Favero Elisa Belluzzi Giovanni Trisolino Mary B Goldring Steven R Goldring Augusto Cigolotti Assunta Pozzuoli Pietro Ruggieri Roberta Ramonda Brunella Grigolo Leonardo Punzi Eleonora Olivotto 《Journal of cellular physiology》2019,234(7):11176-11187
The aim of this study was to identify the molecules and pathways involved in the cross-talk between meniscus and synovium that may play a critical role in osteoarthritis (OA) pathophysiology. Samples of synovium and meniscus were collected from patients with early and end-stage OA and cultured alone or cocultured. Cytokines, chemokines, metalloproteases, and their inhibitors were evaluated at the gene and protein levels. The extracellular matrix (ECM) changes were also investigated. In early OA cultures, higher levels of interleukin-6 (IL-6) and IL-8 messenger RNA were expressed by synovium and meniscus in coculture compared with meniscus cultured alone. RANTES release was significantly increased when the two tissues were cocultured compared with meniscus cultured alone. Increased levels of matrix metalloproteinase-3 (MMP-3) and MMP-10 proteins, as well as increased release of glycosaminoglycans and aggrecan CS846 epitope, were observed when synovium was cocultured with meniscus. In end-stage OA cultures, increased levels of IL-8 and monocyte chemoattractant protein-1 (MCP-1) proteins were released in cocultures compared with cultures of meniscus alone. Chemokine (C-C motif) ligand 21 (CCL21) protein release was higher in meniscus cultured alone and in coculture compared with synovium cultured alone. Increased levels of MMP-3 and 10 proteins were observed when tissues were cocultured compared with meniscus cultured alone. Aggrecan CS846 epitope release was increased in cocultures compared with cultures of either tissue cultured alone. Our study showed the production of inflammatory molecules by synovium and meniscus which could trigger inflammatory signals in early OA patients, and induce ECM loss in the progressive and final stages of OA pathology. 相似文献
130.