全文获取类型
收费全文 | 1883篇 |
免费 | 129篇 |
出版年
2023年 | 4篇 |
2022年 | 24篇 |
2021年 | 31篇 |
2020年 | 16篇 |
2019年 | 21篇 |
2018年 | 31篇 |
2017年 | 12篇 |
2016年 | 51篇 |
2015年 | 100篇 |
2014年 | 95篇 |
2013年 | 112篇 |
2012年 | 155篇 |
2011年 | 160篇 |
2010年 | 103篇 |
2009年 | 85篇 |
2008年 | 85篇 |
2007年 | 104篇 |
2006年 | 81篇 |
2005年 | 86篇 |
2004年 | 108篇 |
2003年 | 78篇 |
2002年 | 83篇 |
2001年 | 49篇 |
2000年 | 44篇 |
1999年 | 41篇 |
1998年 | 20篇 |
1997年 | 13篇 |
1996年 | 17篇 |
1995年 | 12篇 |
1994年 | 6篇 |
1993年 | 12篇 |
1992年 | 20篇 |
1991年 | 17篇 |
1990年 | 12篇 |
1989年 | 20篇 |
1988年 | 13篇 |
1987年 | 10篇 |
1986年 | 10篇 |
1985年 | 8篇 |
1984年 | 9篇 |
1983年 | 3篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1979年 | 5篇 |
1978年 | 5篇 |
1977年 | 7篇 |
1975年 | 10篇 |
1974年 | 4篇 |
1972年 | 2篇 |
1966年 | 2篇 |
排序方式: 共有2012条查询结果,搜索用时 31 毫秒
921.
Young-Hee Jin Wanqiu Hou Hyun Seok Kang Chang-Sung Koh Byung S. Kim 《Journal of virology》2013,87(21):11538-11551
Infection with Theiler''s murine encephalomyelitis virus (TMEV) in the central nervous system (CNS) of susceptible mice results in an immune-mediated demyelinating disease which is considered a relevant viral model of human multiple sclerosis. We previously demonstrated that the expression of positive costimulatory molecules (CD40, CD80, and CD86) is higher on the microglia of TMEV-resistant C57BL/6 (B6) mice than the microglia of TMEV-susceptible SJL/J (SJL) mice. In this study, we analyzed the expression levels of the negative costimulatory molecules PD-1 and PDL-1 in the CNS of TMEV-infected SJL mice and B6 mice. Our results indicated that TMEV infection induces the expression of both PD-1 and PDL-1 on microglia and macrophages in the CNS but not in the periphery. The expression of PD-1 only on CNS-infiltrating macrophages and not on resident microglia was considerably higher (>4-fold) in TMEV-infected SJL mice than TMEV-infected B6 mice. We further demonstrated that interleukn-6 (IL-6) is necessary to induce the maximal expression of PDL-1 but not PD-1 after TMEV infection using IL-6-deficient mice and IL-6-transgenic mice in conjunction with recombinant IL-6. In addition, cells from type I interferon (IFN) receptor knockout mice failed to upregulate PD-1 and PDL-1 expression after TMEV infection in vitro, indicating that type I IFN signaling is associated with the upregulation. However, other IFN signaling may also participate in the upregulation. Taken together, these results strongly suggest that the expression of PD-1 and PDL-1 in the CNS is primarily upregulated following TMEV infection via type I IFN signaling and the maximal expression of PDL-1 additionally requires IL-6 signaling. 相似文献
922.
923.
924.
We report a molecular modelling study to validate the forcefields [condensed-phase optimised molecular potentials for atomistic simulation studies (COMPASS) and polymer-consistent forcefield (PCFF)] in predicting the physical and thermophysical properties of polymers. This work comprises of two key steps: (1) generating and validating the molecular model in predicting the material properties of the bulk amorphous emeraldine base polyaniline and (2) modelling the glass–rubber transition of the polymer. From all the molecular dynamics simulation results, it clearly shows that the more recent COMPASS forcefield provides a higher accuracy in predicting the polymer properties than PCFF, and it enables a more accurate prediction of condensed-phase properties (density, glass transition temperature, solubility parameters, etc.) in a broad range of temperature for various applications. 相似文献
925.
Young Seo Kim Min Young Noh Ji Young Kim Hyun-Jeung Yu Kyung Suk Kim Seung Hyun Kim Seong-Ho Koh 《Molecular neurobiology》2013,47(2):811-820
Mesenchymal stromal cells (MSCs) are emerging as candidate cells for the treatment of neurological diseases because of their neural replacement, neuroprotective, and neurotrophic effects. However, the majority of MSCs transplanted by various routes fail to reach the site of injury, and they have demonstrated only minimal therapeutic benefit in clinical trials. Therefore, enhancing the migration of MSCs to target sites is essential for this therapeutic strategy to be effective. In this study, we assessed whether inhibition of glycogen synthase kinase-3β (GSK-3β) increases the migration capacity of MSCs during ex vivo expansion. Human bone marrow MSCs (hBM-MSCs) were cultured with various GSK-3β inhibitors (LiCl, SB-415286, and AR-A014418). Using a migration assay kit, we found that the motility of hBM-MSCs was significantly enhanced by GSK-3β inhibition. Western blot analysis revealed increased levels of migration-related signaling proteins such as phospho-GSK-3β, β-catenin, phospho-c-Raf, phospho-extracellular signal-regulated kinase (ERK), phospho-β-PAK-interacting exchange factor (PIX), and CXC chemokine receptor 4 (CXCR4). In addition, real-time polymerase chain reaction demonstrated increased expression of matrix metalloproteinase-2 (MMP-2), membrane-type MMP-1 (MT1-MMP), and β-PIX. In the reverse approach, treatment with β-PIX shRNA or CXCR4 inhibitor (AMD 3100) reduced hBM-MSC migration. These findings suggest that inhibition of GSK-3β during ex vivo expansion of hBM-MSCs may enhance their migration capacity by increasing expression of β-catenin, phospho-c-Raf, phospho-ERK, and β-PIX and the subsequent up-regulation of CXCR4. Enhancing the migration capacity of hBM-MSCs by treating these cells with GSK-3β inhibitors may increase their therapeutic potential. 相似文献
926.
Mi Nam Lee Ara Koh Dohyun Park Jin-Hyeok Jang Dongoh Kwak Hyeona Jeon Jaeyoon Kim Eun-Jeong Choi Heeyoon Jeong Pann-Ghill Suh Sung Ho Ryu 《Cellular signalling》2013,25(2):539-551
Ras homolog enriched in brain (Rheb) regulates diverse cellular functions by modulating its nucleotide-bound status. Although Rheb contains a high basal GTP level, the regulatory mechanism of Rheb is not well understood. In this study, we propose soluble αβ-tubulin acts as a constitutively active Rheb activator, which may explain the reason why Rheb has a high basal GTP levels. We found that soluble αβ-tubulin is a direct Rheb-binding protein and that its deacetylated form has a high binding affinity for Rheb. Modulation of both soluble and acetylated αβ-tubulin levels affects the level of GTP-bound Rheb. This occurs in the mitotic phase in which the level of acetylated αβ-tubulin is increased but that of GTP-bound Rheb is decreased. Constitutively active Rheb-overexpressing cells showed an abnormal mitotic progression, suggesting the deacetylated αβ-tubulin-mediated regulation of Rheb status may be important for proper mitotic progression. Taken together, we propose that deacetylated soluble αβ-tubulin is a novel type of positive regulator of Rheb and may play a role as a temporal regulator for Rheb during the cell cycle. 相似文献
927.
Motor maps and electrical thresholds for evoking movements from motor areas of the cerebral cortex were evaluated in normal cats by using intracortical microstimulation techniques. Stainless steel chambers were implanted over craniotomies in adult cats trained to perform reaching and retrieval movements with their forelimbs. Prehensile motor training was continued and movement performance monitored for about 6–10 weeks during which the cortex was progressively explored with sharp tungsten electrodes inserted into cortical gyri (anterior and posterior sigmoid, and coronal) and the banks of sulci (cruciate, presylvian and coronal). Twice weekly, under light general anaesthesia, 3–4 tracks were made in either hemisphere till about 50 tracks were made in each hemisphere. Mean thresholds for evoking forelimb movements from different cytoarchitectonic areas (4γ, 4δ, 6aγ and 3a) were compared and no consistent or significant differences were observed between the different areas. In the animals (4/6) which used either forelimb to perform the tasks, there were no consistent differences in the mean thresholds for evoking forelimb movements from the two hemispheres. However, in 2 animals, which used their right forelimbs predominantly or exclusively to perform all the tasks, mean thresholds for evoking forelimb movements was significantly higher in areas 4γ and 6aγ of the left hemisphere (compared to the right); no consistent differences in the mean thresholds for evoking hindlimb or facial movements were observed between the two hemispheres. These findings suggest that ICMS thresholds for evoking forelimb movements may be similar in different sensorimotor areas of the cat cerebral cortex, and these thresholds could be influenced by motor training. 相似文献
928.
929.
930.
Soon Young Shin Hyuk Yoon Doseok Hwang Seunghyun Ahn Dong-Wook Kim Dongsoo Koh Young Han Lee Yoongho Lim 《Bioorganic & medicinal chemistry》2013,21(22):7018-7024
Colorectal cancer is the third and fourth leading cause of cancer in males and females, respectively. Flavonoids, including chalcones, are secondary metabolites in plants that exhibit diverse biological activities, including antibacterial, antimalarial, and antitumor activities. In order to find potent and novel chemotherapy drugs for colorectal cancer, a series of benzochalcone derivatives, in which an α,β-unsaturated carbonyl group was replaced with a pyrazoline, was designed and synthesized. A clonogenic survival assay was performed with each derivative to evaluate antitumor activity. 1-(5-(2,4-Dimethoxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl)naphthalen-2-ol (derivative 7) had the most potent inhibitory effect on the long-term clonogenicity of HCT116 human colorectal cancer cells (IC50 = 2.4 μM). The results of Western blot and flow cytometric analyses suggested that derivative 7 could inhibit the proliferation of colorectal cancer cells through inhibition of cell cycle progression and induction of apoptosis. To elucidate its molecular mechanism, in vitro kinase binding assays were carried out, which demonstrated that derivative 7 inhibited aurora kinases A and B selectively. The binding modes between the compound and aurora kinases were interpreted using in silico docking experiments to explain the selective inhibitory effects on aurora kinases A and B. These findings will facilitate the design of potent novel benzochalcones as anticancer agents. 相似文献