全文获取类型
收费全文 | 182999篇 |
免费 | 9621篇 |
国内免费 | 8269篇 |
出版年
2023年 | 1279篇 |
2022年 | 2975篇 |
2021年 | 5403篇 |
2020年 | 3733篇 |
2019年 | 4622篇 |
2018年 | 5247篇 |
2017年 | 4248篇 |
2016年 | 7204篇 |
2015年 | 12507篇 |
2014年 | 13335篇 |
2013年 | 13417篇 |
2012年 | 14063篇 |
2011年 | 10591篇 |
2010年 | 7116篇 |
2009年 | 6685篇 |
2008年 | 5893篇 |
2007年 | 5098篇 |
2006年 | 4436篇 |
2005年 | 9613篇 |
2004年 | 7751篇 |
2003年 | 5776篇 |
2002年 | 2910篇 |
2001年 | 2618篇 |
2000年 | 1737篇 |
1999年 | 2948篇 |
1998年 | 1202篇 |
1997年 | 1105篇 |
1996年 | 959篇 |
1995年 | 962篇 |
1994年 | 863篇 |
1992年 | 2623篇 |
1991年 | 2564篇 |
1990年 | 2541篇 |
1989年 | 2340篇 |
1988年 | 2237篇 |
1987年 | 2036篇 |
1986年 | 1809篇 |
1985年 | 1877篇 |
1984年 | 1214篇 |
1983年 | 951篇 |
1979年 | 1092篇 |
1978年 | 761篇 |
1975年 | 873篇 |
1974年 | 994篇 |
1973年 | 1006篇 |
1972年 | 954篇 |
1971年 | 928篇 |
1970年 | 820篇 |
1969年 | 830篇 |
1967年 | 751篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
51.
52.
53.
Indomethacin and substance BW-755C in experiments on isolated myometrium striae of pregnant white rats exert an inhibiting effect on the contractile uterus function due to inhibition of cyclooxygenase or lipoxygenase ways of the arachidonic acid transformation. Prostaglandin F2 alpha is sensitive to functioning of the cyclooxygenase and lipoxygenase ways of the arachidonic acid transformation, while oxytocin--only lipoxygenase one. Conclusions rest on results from multiparametric analysis of the contractile uterus function suggested by authors and confirmed by the pattern recognition method--the Karunen-Loev orthogonal decomposition. 相似文献
54.
55.
Assessment of uncoupling activity of uncoupling protein 3 using a yeast heterologous expression system. 总被引:2,自引:0,他引:2
Uncoupling protein 3L, uncoupling protein 1 and the mitochondrial oxoglutarate carrier were expressed in Saccharomyces cerevisae. Effects on different parameters related to the energy expenditure were studied. Both uncoupling protein 3L and uncoupling protein 1 reduced the growth rate by 49% and 32% and increased the whole yeast O2 consumption by 31% and 19%, respectively. In isolated mitochondria, uncoupling protein 1 increased the state 4 respiration by 1.8-fold, while uncoupling protein 3L increased the state 4 respiration by 1.2-fold. Interestingly, mutant uncoupling protein 1 carrying the H145Q and H147N mutations, previously shown to markedly decrease the H+ transport activity of uncoupling protein 1 when assessed using a proteoliposome system (Bienengraeber et al. (1998) Biochem. 37, 3-8), uncoupled the mitochondrial respiration to almost the same degree as wild-type uncoupling protein 1. Thus, absence of this histidine pair in uncoupling protein 2 and uncoupling protein 3 does not by itself rule out the possibility that these carriers have an uncoupling function. The oxoglutarate carrier had no effect on any of the studied parameters. In summary, a discordance exists between the magnitude of effects of uncoupling protein 3L and uncoupling protein 1 in whole yeast versus isolated mitochondria, with uncoupling protein 3L having greater effects in whole yeast and a smaller effect on the state 4 respiration in isolated mitochondria. These findings suggest that uncoupling protein 3L, like uncoupling protein 1, has an uncoupling activity. However, the mechanism of action and/or regulation of the activity of uncoupling protein 3L is likely to be different. 相似文献
56.
Li Zhang Mark Morrison Páraic ó Cuív Paul Evans Claire M. Rickard 《Journal of bacteriology》2012,194(23):6639
In recent years, Staphylococcus epidermidis has become a major nosocomial pathogen and the most common cause of intravascular catheter-related bacteremia, which can increase morbidity and mortality and significantly affect patient recovery. We report a draft genome sequence of Staphylococcus epidermidis AU12-03, isolated from an intravascular catheter tip. 相似文献
57.
Tao Tian Danhua Yao Lei Zheng Zhiyuan Zhou Yantao Duan Bin Liu Pengfei Wang Yousheng Li 《Cell death & disease》2020,11(12)
Previously, we confirmed that sphingosine kinase 1 (SphK1) inhibition improves sepsis-associated liver injury. High-mobility group box 1 (HMGB1) translocation participates in the development of acute liver failure. However, little information is available on the association between SphK1 and HMGB1 translocation during sepsis-associated liver injury. In the present study, we aimed to explore the effect of SphK1 inhibition on HMGB1 translocation and the underlying mechanism during sepsis-associated liver injury. Primary Kupffer cells and hepatocytes were isolated from SD rats. The rat model of sepsis-associated liver damage was induced by intraperitoneal injection with lipopolysaccharide (LPS). We confirmed that Kupffer cells were the cells primarily secreting HMGB1 in the liver after LPS stimulation. LPS-mediated HMGB1 expression, intracellular translocation, and acetylation were dramatically decreased by SphK1 inhibition. Nuclear histone deacetyltransferase 4 (HDAC4) translocation and E1A-associated protein p300 (p300) expression regulating the acetylation of HMGB1 were also suppressed by SphK1 inhibition. HDAC4 intracellular translocation has been reported to be controlled by the phosphorylation of HDAC4. The phosphorylation of HDAC4 is modulated by CaMKII-δ. However, these changes were completely blocked by SphK1 inhibition. Additionally, by performing coimmunoprecipitation and pull-down assays, we revealed that SphK1 can directly interact with CaMKII-δ. The colocalization of SphK1 and CaMKII-δ was verified in human liver tissues with sepsis-associated liver injury. In conclusion, SphK1 inhibition diminishes HMGB1 intracellular translocation in sepsis-associated liver injury. The mechanism is associated with the direct interaction of SphK1 and CaMKII-δ.Subject terms: Hepatotoxicity, Sepsis 相似文献
58.
59.
M Kh Ga?nutdinov S I Mirmakhmudova N M Mullagalieva Ia Kh Turakulov 《Biulleten' eksperimental'no? biologii i meditsiny》1984,97(3):293-295
Addition of a thermostable cytoplasmic fraction leads to the uncoupling of oxidative phosphorylation of the mitochondria. In hyperthyrosis such an effect manifests itself more powerfully than in the control. Addition of the thermostable cytoplasmic fraction induces electrogenic phosphate transport via the mitochondrial membrane. In hyperthyrosis, the activity of the thermostable inducer of phosphate transport in the cytoplasm increases. The functioning of the phosphate cycle may be the cause of the uncoupling of oxidative phosphorylation of the mitochondria during the disease in question. 相似文献
60.
Thyroid hormones are potent, instantaneous, and reversible inhibitors of ethanol oxidation catalyzed by isozymes of class I and II human alcohol dehydrogenase (ADH). None of the thyroid hormones inhibits class III ADH. At pH 7.40 the apparent Ki values vary between 55 and 110 microM for triiodothyronine, 35 and greater than 200 microM for thyroxine, and 10 and 23 microM for triiodothyroacetic acid. The inhibition is of a mixed type toward both NAD+ and ethanol. The binding of the thyroid hormone triiodothyronine to beta 1 gamma 1 ADH is mutually exclusive with 1,10-phenanthroline, 4-methylpyrazole, and testosterone, identifying a binding site(s) for the thyroid hormones, which overlap(s) both the 1,10-phenanthroline site near the active site zinc atom and the testosterone binding site, the latter being a regulatory site on the gamma-subunit-containing isozymes and distinct from their catalytic site. The inhibition by thyroid hormones may have implications for regulation of ADH catalysis of ethanol and alcohols in the intermediary metabolism of dopamine, norepinephrine, and serotonin and in steroid metabolism. In concert with other hormonal regulators, e.g., testosterone, the rate of ADH catalysis is capable of being fine tuned in accord with both substrate and modulator concentrations. 相似文献