全文获取类型
收费全文 | 1733篇 |
免费 | 197篇 |
国内免费 | 46篇 |
出版年
2024年 | 3篇 |
2023年 | 33篇 |
2022年 | 58篇 |
2021年 | 93篇 |
2020年 | 106篇 |
2019年 | 138篇 |
2018年 | 84篇 |
2017年 | 61篇 |
2016年 | 60篇 |
2015年 | 80篇 |
2014年 | 86篇 |
2013年 | 115篇 |
2012年 | 73篇 |
2011年 | 75篇 |
2010年 | 59篇 |
2009年 | 55篇 |
2008年 | 63篇 |
2007年 | 64篇 |
2006年 | 48篇 |
2005年 | 41篇 |
2004年 | 49篇 |
2003年 | 61篇 |
2002年 | 29篇 |
2001年 | 28篇 |
2000年 | 34篇 |
1999年 | 28篇 |
1998年 | 41篇 |
1997年 | 29篇 |
1996年 | 38篇 |
1995年 | 21篇 |
1994年 | 19篇 |
1993年 | 20篇 |
1992年 | 38篇 |
1991年 | 24篇 |
1990年 | 18篇 |
1989年 | 13篇 |
1988年 | 15篇 |
1987年 | 11篇 |
1986年 | 12篇 |
1985年 | 15篇 |
1984年 | 9篇 |
1983年 | 6篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1976年 | 3篇 |
1975年 | 3篇 |
排序方式: 共有1976条查询结果,搜索用时 15 毫秒
51.
The enantiomers of formoterol (R;R and S;S) and their diastereomers (R;S and S;R) were synthesized and purified using a new procedure which required the preparation of the (R;R)- and (S;S)-forms of N-(1-phenylethyl)-N-(1-(p-methoxyphenyl)-2-propyl)-amine as important intermediates. The enantiomeric purity obtained was greater than 99.3%, usually greater than 99.7%. The four stereoisomers were examined with respect to their ability to interact in vitro with beta-adrenoceptors in tissues isolated from guinea pig. The effects measured were (1) relaxation of the tracheal smooth muscle (mostly beta 2), (2) depression of subtetanic contractions of the soleus muscle (beta 2), and (3) increase in the force of the papillary muscle of the left ventricle of the heart (beta 1). All enantiomers caused a concentration-dependent and complete relaxation of the tracheal smooth muscle which was inhibited by propranolol. The order of potency was (R;R) much greater than (R;S) = (S;R) greater than (S;S). There was a 1,000-fold difference in potency between the most and the least potent isomer. The presence of the (S;S)-isomer did not affect the activity of the (R;R)-isomer on the tracheal smooth muscle. Also on the skeletal and cardiac muscles (R;R)-formoterol was more potent than its (R;S)-isomer. The selectivity for beta 2-adrenoceptors appeared to be slightly higher for the (R;R)-isomer than for the (R;S)-isomer. The potency of the (S;R)- and (S;S)-isomers on the papillary muscle was too low to be determined accurately.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
52.
Summary Previous work has suggested that subcultivated human fetal heart muscle cell cultures contain immature cardiac muscle cells
capable only of limited differentiation after mitogen withdrawal. We studied several human fetal heart cultures (14–15 wk
gestation) at several passage levels using immunocytochemistry, autoradiography, and Northern blot analysis. Characteristics
in high-mitogen (growth) medium were compared with those after serum withdrawal. Cultured cells from one heart, expanded through
2 passages in growth medium, did not beat; however, 75% of cells did beat after subsequent culture for 24 days in low-serum
(differentiation) medium containing insulin. In confluent cultures after 1 passage, there was no detectable difference in
the number of cardiac myocytes present in growth medium compared with that 7 days after serum withdrawal. After 4 passages,
however, serum withdrawal increased the number of cells expressing immunoreactive sarcomeric myosin heavy chain by 100-fold;
expression of immunoreactive sarcomeric actin andα-cardiac actin mRNA also increased in the same cultures. Similar results were obtained in cultures kept in differentiation
medium for 20 days before passage and expansion in growth medium. Using isopycinc centrifugation, a high-density cell fraction
was isolated which contained no immunostained myocytes in growth medium but numerous myocytes after serum withdrawal. Combined
immunocytochemistry/autoradiography showed that myocytes synthesize DNA in growth medium and in serum-free medium containing
fibroblast growth factor, but not in serum-free medium alone. The results indicate that a) human fetal cardiac muscle cells
proliferate in vitro and can maintain a phenotype characteristic of fetal myocytes after multiple subcultivations followed
by serum withdrawal; b) after subcultivation in growth medium, some myocytes modulate their phenotype into one in which detectable
levels of cardiac contractile proteins are expressed only after mitogen withdrawal, and c) the phenotype attained after serum
withdrawal is in part dependent on passage level. Cultured human fetal myocardial cells my provide a useful experimental system
for the study of human cardiac muscle cell biology. 相似文献
53.
ZAKβ antagonizes and ameliorates the cardiac hypertrophic and apoptotic effects induced by ZAKα 下载免费PDF全文
Chien‐Yao Fu Wei‐Wen Kuo Tsung‐Jung Ho Su‐Ying Wen Ling‐Chun Lin Yan‐Shen Tseng Hui‐Chuan Hung Vijaya Padma Viswanadha Chih‐Yang Huang 《Cell biochemistry and function》2016,34(8):606-612
ZAK (sterile alpha motif and leucine zipper containing kinase AZK), a serine/threonine kinase with multiple biochemical functions, has been associated with various cell processes, including cell proliferation, cell differentiation, and cardiac hypertrophy. In our previous reports, we found that the activation of ZAKα signaling was critical for cardiac hypertrophy. In this study, we show that the expression of ZAKα activated apoptosis through both a FAS‐dependent pathway and a mitochondria‐dependent pathway by subsequently inducing caspase‐3. ZAKβ, an isoform of ZAKα, is dramatically expressed during cardiac hypertrophy and apoptosis. The interaction between ZAKα and ZAKβ was demonstrated here using immunoprecipitation. The results show that ZAKβ has the ability to diminish the expression level of ZAKα. These findings reveal an inherent regulatory role of ZAKβ to antagonize ZAKα and to subsequently downregulate the cardiac hypertrophy and apoptosis induced by ZAKα. 相似文献
54.
Boquan Wu Shilong You Hao Qian Shaojun Wu Saien Lu Ying Zhang Yingxian Sun Naijin Zhang 《Journal of cellular and molecular medicine》2021,25(14):6470-6478
At present, cardiovascular disease is one of the important factors of human death, and there are many kinds of proteins involved. Sirtuins family proteins are involved in various physiological and pathological activities of the human body. Among them, there are more and more studies on the relationship between sirtuin2 (SIRT2) protein and cardiovascular diseases. SIRT2 can effectively inhibit pathological cardiac hypertrophy. The effect of SIRT2 on ischaemia-reperfusion injury has different effects under different conditions. SIRT2 can reduce the level of reactive oxygen species (ROS), which may help to reduce the severity of diabetic cardiomyopathy. SIRT2 can affect a variety of cardiovascular diseases, energy metabolism and the ageing of cardiomyocytes, thereby affecting heart failure. SIRT2 also plays an important role in vascular disease. For endothelial cell damage used by oxidative stress, the role of SIRT2 is bidirectional, which is related to the degree of oxidative stress stimulation. When the degree of stimulation is small, SIRT2 plays a protective role, and when the degree of stimulation increases to a certain level, SIRT2 plays a negative role. In addition, SIRT2 is also involved in the remodelling of blood vessels and the repair of skin damage. 相似文献
55.
Luocheng Lv Zhaofu Liao Jiali Luo Hongyi Chen Hongyan Guo Jifeng Yang Ruijin Huang Qin Pu Hui Zhao Ziqiang Yuan Shanshan Feng Xufeng Qi Dongqing Cai 《Journal of cellular and molecular medicine》2020,24(4):2531-2541
Recent research has revealed that cardiac telocytes (CTs) play an important role in cardiac physiopathology and the regeneration of injured myocardium. Recently, we reported that the adult Xenopus tropicalis heart can regenerate perfectly in a nearly scar‐free manner after injury via apical resection. However, whether telocytes exist in the X tropicalis heart and are affected in the regeneration of injured X tropicalis myocardium is still unknown. The present ultrastructural and immunofluorescent double staining results clearly showed that CTs exist in the X tropicalis myocardium. CTs in the X tropicalis myocardium were mainly twined around the surface of cardiomyocyte trabeculae and linked via nanocontacts between the ends of the telopodes, forming a three‐dimensional network. CTs might play a role in the regeneration of injured myocardium. 相似文献
56.
Felicia Carotenuto Laura Teodori Anna Maria Maccari Luciano Delbono Giuseppe Orlando Paolo Di Nardo 《Journal of cellular and molecular medicine》2020,24(5):2704-2716
Regenerative therapies including stem cell treatments hold promise to allow curing patients affected by severe cardiac muscle diseases. However, the clinical efficacy of stem cell therapy remains elusive, so far. The two key roadblocks that still need to be overcome are the poor cell engraftment into the injured myocardium and the limited knowledge of the ideal mixture of bioactive factors to be locally delivered for restoring heart function. Thus, therapeutic strategies for cardiac repair are directed to increase the retention and functional integration of transplanted cells in the damaged myocardium or to enhance the endogenous repair mechanisms through cell-free therapies. In this context, biomaterial-based technologies and tissue engineering approaches have the potential to dramatically impact cardiac translational medicine. This review intends to offer some consideration on the cell-based and cell-free cardiac therapies, their limitations and the possible future developments. 相似文献
57.
Chuan Li Zhaonan Sun Fang Yuan Zhicheng Zhao Jiehong Zhang Baotong Zhang Hongyue Li Tong Liu Xiangchen Dai 《Journal of cellular and molecular medicine》2020,24(6):3438-3448
Indoleamine 2, 3-dioxygenase (IDO)-mediated regulation of tryptophan metabolism plays an important role in immune tolerance in transplantation, but it has not been elucidated which mechanism specifically induces the occurrence of immune tolerance. Our study revealed that IDO exerts immunosuppressive effects through two pathways in mouse heart transplantation, ‘tryptophan depletion’ and ‘tryptophan metabolite accumulation’. The synergism between IDO+DC and TC (tryptophan catabolic products) has stronger inhibitory effects on T lymphocyte proliferation and mouse heart transplant rejection than the two intervention factors alone, and significantly prolong the survival time of donor-derived transplanted skin. This work demonstrates that the combination of IDO+DC and TC can induce immune tolerance to a greater extent, and reduce the rejection of transplanted organs. 相似文献
58.
59.
Qingxia Fang Ting Liu Chenhuan Yu Xiuli Yang Yanfei Shao Jiana Shi Xiaolan Ye Xiaochun Zheng Jieping Yan Danfeng Xu Xiaozhou Zou 《Journal of cellular and molecular medicine》2020,24(6):3678-3691
The current study was designed to explore the role and underlying mechanism of lncRNA taurine up-regulated gene 1 (TUG1) in cardiac hypertrophy. Mice were treated by transverse aortic constriction (TAC) surgery to induce cardiac hypertrophy, and cardiomyocytes were treated by phenylephrine (PE) to induce hypertrophic phenotype. Haematoxylin-eosin (HE), wheat germ agglutinin (WGA) and immunofluorescence (IF) were used to examine morphological alterations. Real-time PCR, Western blots and IF staining were used to detect the expression of RNAs and proteins. Luciferase assay and RNA pull-down assay were used to verify the interaction. It is revealed that TUG1 was up-regulated in the hearts of mice treated by TAC surgery and in PE-induced cardiomyocytes. Functionally, overexpression of TUG1 alleviated cardiac hypertrophy both in vivo and in vitro. Mechanically, TUG1 sponged and sequestered miR-34a to increase the Dickkopf 1 (DKK1) level, which eventually inhibited the activation of Wnt/β-catenin signalling. In conclusion, the current study reported the protective role and regulatory mechanism of TUG1 in cardiac hypertrophy and suggested that TUG1 may serve as a novel molecular target for treating cardiac hypertrophy. 相似文献
60.
Xiuxiang Liu Jinjin Wu Chenying Zhu Jie Liu Xiaoli Chen Tao Zhuang Yashu Kuang Yanfang Wang Hao Hu Ping Yu Huimin Fan Yuzhen Zhang Zhongmin Liu Lin Zhang 《Journal of cellular and molecular medicine》2020,24(2):2013-2026
Cardiac vascular microenvironment is crucial for cardiac remodelling during the process of heart failure. Sphingosine 1‐phosphate (S1P) tightly regulates vascular homeostasis via its receptor, S1pr1. We therefore hypothesize that endothelial S1pr1 might be involved in pathological cardiac remodelling. In this study, heart failure was induced by transverse aortic constriction (TAC) operation. S1pr1 expression is significantly increased in microvascular endothelial cells (ECs) of post‐TAC hearts. Endothelial‐specific deletion of S1pr1 significantly aggravated cardiac dysfunction and deteriorated cardiac hypertrophy and fibrosis in myocardium. In vitro experiments demonstrated that S1P/S1pr1 praxis activated AKT/eNOS signalling pathway, leading to more production of nitric oxide (NO), which is an essential cardiac protective factor. Inhibition of AKT/eNOS pathway reversed the inhibitory effect of EC‐S1pr1‐overexpression on angiotensin II (AngII)‐induced cardiomyocyte (CM) hypertrophy, as well as on TGF‐β‐mediated cardiac fibroblast proliferation and transformation towards myofibroblasts. Finally, pharmacological activation of S1pr1 ameliorated TAC‐induced cardiac hypertrophy and fibrosis, leading to an improvement in cardiac function. Together, our results suggest that EC‐S1pr1 might prevent the development of pressure overload‐induced heart failure via AKT/eNOS pathway, and thus pharmacological activation of S1pr1 or EC‐targeting S1pr1‐AKT‐eNOS pathway could provide a future novel therapy to improve cardiac function during heart failure development. 相似文献