全文获取类型
收费全文 | 463篇 |
免费 | 35篇 |
国内免费 | 1篇 |
专业分类
499篇 |
出版年
2022年 | 3篇 |
2021年 | 7篇 |
2020年 | 3篇 |
2019年 | 6篇 |
2018年 | 7篇 |
2017年 | 9篇 |
2016年 | 7篇 |
2015年 | 26篇 |
2014年 | 15篇 |
2013年 | 26篇 |
2012年 | 32篇 |
2011年 | 39篇 |
2010年 | 15篇 |
2009年 | 24篇 |
2008年 | 12篇 |
2007年 | 26篇 |
2006年 | 31篇 |
2005年 | 28篇 |
2004年 | 25篇 |
2003年 | 24篇 |
2002年 | 16篇 |
2001年 | 10篇 |
2000年 | 14篇 |
1999年 | 11篇 |
1998年 | 11篇 |
1997年 | 3篇 |
1996年 | 4篇 |
1995年 | 3篇 |
1994年 | 10篇 |
1992年 | 6篇 |
1991年 | 5篇 |
1990年 | 3篇 |
1989年 | 5篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1986年 | 4篇 |
1985年 | 4篇 |
1984年 | 5篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1973年 | 1篇 |
1972年 | 3篇 |
1971年 | 1篇 |
排序方式: 共有499条查询结果,搜索用时 0 毫秒
101.
Changes of lipase-catalyzed lipolytic rates in a batch reactor 总被引:1,自引:0,他引:1
A dramatic change of the reaction rate was observed for the lipase-catalyzed hyrolysis of tributyrin in a batch reactor. Immediately after the addition of the enzyme, the lipolysis rate increased continuously until a maximal reaction rate was reached. The duration of the induction was mainly controlled by the bulk enzyme concentration and the reactor stirring speed. The reaction rate dropped sharply after reaching its maximal value. The lipolysis decayed at a rate of about 0.012 min(-1), and was not affected by changes of the stirring speed. This decay was attributed to the fast deactivation of the surface-adsorbed lipase, and possibly to the extremely slow desorption of the inactivated species. For reaction time longer than 120 minutes, the lipolysis decreased at a much slower rate. Several mechanisms for the decay of the lipolysis rate were discussed. 相似文献
102.
103.
Stereochemical course of thiophosphoryl group transfer catalyzed by mitochondrial phosphoenolpyruvate carboxykinase 总被引:1,自引:0,他引:1
K F Sheu H T Ho L D Nolan P Markovitz J P Richard M F Utter P A Frey 《Biochemistry》1984,23(8):1779-1783
Guinea pig liver mitochondrial phosphoenolpyruvate carboxykinase catalyzes the conversion of (Rp)-guanosine 5'-(3-thio[3-18O]triphosphate) and oxalacetate to (Sp)-[18O] thiophosphoenolpyruvate , GDP, and CO2 by a mechanism that involves overall inversion in the configuration of the chiral [18O]thiophosphate group. This result is most consistent with a single displacement mechanism in which the [18O]thiophosphoryl group is transferred from (Rp)-guanosine 5'-(3-thio[3-18O]triphosphate) bound at the active site directly to enolpyruvate generated at the active site by the decarboxylation of oxalacetate. In particular, this result does not indicate the involvement of a covalent thiophosphoryl-enzyme on the reaction pathway. 相似文献
104.
Cheng SL Liu RH Sheu JN Chen ST Sinchaikul S Tsay GJ 《Journal of biomedical science》2007,14(1):87-105
Although arbutin is a natural product and widely used as an ingredient in skin care products, its effect on the gene expression level of human skin with malignant melanoma cells is rarely reported. We aim to investigate the genotoxic effect of arbutin on the differential gene expression profiling in A375 human malignant melanoma cells through its effect on tumorigenesis and related side-effect. The DNA microarray analysis provided the differential gene expression pattern of arbutin-treated A375 cells with the significant changes of 324 differentially expressed genes, containing 88 up-regulated genes and 236 down-regulated genes. The gene ontology of differentially expressed genes was classified as belonging to cellular component, molecular function and biological process. In addition, four down-regulated genes of AKT1, CLECSF7, FGFR3, and LRP6 served as candidate genes and correlated to suppress the biological processes in the cell cycle of cancer progression and in the downstream signaling pathways of malignancy of melanocytic tumorigenesis. 相似文献
105.
YenDun Tony Tzeng KuanHao Tsui LingMing Tseng MingFeng Hou PeiYi Chu Jim JinnChyuan Sheu ChiaJung Li 《Journal of cellular and molecular medicine》2022,26(14):4007
The discovery of early diagnosis and prognostic markers for breast cancer can significantly improve survival and reduce mortality. LSM1 is known to be involved in the general process of mRNA degradation in complexes containing LSm subunits, but the molecular and biological functions in breast cancer remain unclear. Here, the expression of LSM1 mRNA in breast cancer was estimated using The Cancer Genome Atlas (TCGA), Oncomine, TIMER and bc‐GenExMiner databases. We found that functional LSM1 inactivation caused by mutations and profound deletions predicted poor prognosis in breast cancer (BRCA) patients. LSM1 was highly expressed in both BRCA tissues and cells compared to normal breast tissues/cells. High LSM1 expression is associated with poorer overall survival and disease‐free survival. The association between LSM1 and immune infiltration of breast cancer was assessed by TIMER and CIBERSORT algorithms. LSM1 showed a strong correlation with various immune marker sets. Most importantly, pharmacogenetic analysis of BRCA cell lines revealed that LSM1 inactivation was associated with increased sensitivity to refametinib and trametinib. However, both drugs could mimic the effects of LSM1 inhibition and their drug sensitivity was associated with MEK molecules. Therefore, we investigated the clinical application of LSM1 to provide a basis for sensitive diagnosis, prognosis and targeted treatment of breast cancer. 相似文献
106.
Spa2p Interacts with Cell Polarity Proteins and Signaling Components Involved in Yeast Cell Morphogenesis 总被引:22,自引:3,他引:22 下载免费PDF全文
Yi-Jun Sheu Beatriz Santos Nathalie Fortin Christine Costigan Michael Snyder 《Molecular and cellular biology》1998,18(7):4053-4069
The yeast protein Spa2p localizes to growth sites and is important for polarized morphogenesis during budding, mating, and pseudohyphal growth. To better understand the role of Spa2p in polarized growth, we analyzed regions of the protein important for its function and proteins that interact with Spa2p. Spa2p interacts with Pea2p and Bud6p (Aip3p) as determined by the two-hybrid system; all of these proteins exhibit similar localization patterns, and spa2Δ, pea2Δ, and bud6Δ mutants display similar phenotypes, suggesting that these three proteins are involved in the same biological processes. Coimmunoprecipitation experiments demonstrate that Spa2p and Pea2p are tightly associated with each other in vivo. Velocity sedimentation experiments suggest that a significant portion of Spa2p, Pea2p, and Bud6p cosediment, raising the possibility that these proteins form a large, 12S multiprotein complex. Bud6p has been shown previously to interact with actin, suggesting that the 12S complex functions to regulate the actin cytoskeleton. Deletion analysis revealed that multiple regions of Spa2p are involved in its localization to growth sites. One of the regions involved in Spa2p stability and localization interacts with Pea2p; this region contains a conserved domain, SHD-II. Although a portion of Spa2p is sufficient for localization of itself and Pea2p to growth sites, only the full-length protein is capable of complementing spa2 mutant defects, suggesting that other regions are required for Spa2p function. By using the two-hybrid system, Spa2p and Bud6p were also found to interact with components of two mitogen-activated protein kinase (MAPK) pathways important for polarized cell growth. Spa2p interacts with Ste11p (MAPK kinase [MEK] kinase) and Ste7p (MEK) of the mating signaling pathway as well as with the MEKs Mkk1p and Mkk2p of the Slt2p (Mpk1p) MAPK pathway; for both Mkk1p and Ste7p, the Spa2p-interacting region was mapped to the N-terminal putative regulatory domain. Bud6p interacts with Ste11p. The MEK-interacting region of Spa2p corresponds to the highly conserved SHD-I domain, which is shown to be important for mating and MAPK signaling. spa2 mutants exhibit reduced levels of pheromone signaling and an elevated level of Slt2p kinase activity. We thus propose that Spa2p, Pea2p, and Bud6p function together, perhaps as a complex, to promote polarized morphogenesis through regulation of the actin cytoskeleton and signaling pathways. 相似文献
107.
Identification of a ryanodine receptor in rat heart mitochondria 总被引:8,自引:0,他引:8
Beutner G Sharma VK Giovannucci DR Yule DI Sheu SS 《The Journal of biological chemistry》2001,276(24):21482-21488
Recent studies have shown that, in a wide variety of cells, mitochondria respond dynamically to physiological changes in cytosolic Ca(2+) concentrations ([Ca(2+)](c)). Mitochondrial Ca(2+) uptake occurs via a ruthenium red-sensitive calcium uniporter and a rapid mode of Ca(2+) uptake. Surprisingly, the molecular identity of these Ca(2+) transport proteins is still unknown. Using electron microscopy and Western blotting, we identified a ryanodine receptor in the inner mitochondrial membrane with a molecular mass of approximately 600 kDa in mitochondria isolated from the rat heart. [(3)H]Ryanodine binds to this mitochondrial ryanodine receptor with high affinity. This binding is modulated by Ca(2+) but not caffeine and is inhibited by Mg(2+) and ruthenium red in the assay medium. In the presence of ryanodine, Ca(2+) uptake into isolated heart mitochondria is suppressed. In addition, ryanodine inhibited mitochondrial swelling induced by Ca(2+) overload. This swelling effect was not observed when Ca(2+) was applied to the cytosolic fraction containing sarcoplasmic reticulum. These results are the first to identify a mitochondrial Ca(2+) transport protein that has characteristics similar to the ryanodine receptor. This mitochondrial ryanodine receptor is likely to play an essential role in the dynamic uptake of Ca(2+) into mitochondria during Ca(2+) oscillations. 相似文献
108.
Trastuzumab is used for breast cancer patients with high expression levels of HER2 (human epidermal growth factor receptor 2)/neu; however, it has no effect on cancers with low levels of HER2/neu. SM (solamargine), a major steroidal alkaloid glycoside purified from Solanum incanum, triggered apoptosis of breast cancer cells (MCF-7 and SK-BR-3 cells) and non-cancerous breast epithelial cells (HBL-100 cells) within 3 h. To extend the application of trastuzumab in breast cancer patients, the regulation of HER2/neu expression by SM was investigated. SM significantly up-regulates HER2/neu expression in breast cancer cells with low and high expression levels of HER2/neu, and synergistically enhanced the effect of trastuzumab in inhibiting cell proliferation. Additionally, HER2/neu and TOP2A [TopoII (topoisomerase II) alpha] genes share the same amplicon on an identical chromosome. Notably, SM co-regulates HER2/neu and TopoIIalpha expression markedly, and enhances TopoII inhibitor-EPI (epirubicin)-induced cytotoxicity to breast cancer cells. 相似文献
109.
Wan‐Jung Lu Kuan‐Hung Lin Mei‐Fang Tseng Kuo‐Ching Yuan Hung‐Chang Huang Joen‐Rong Sheu Ray‐Jade Chen 《Journal of cellular and molecular medicine》2019,23(3):1723-1734
Haemorrhagic shock and resuscitation (HS/R) may cause global ischaemia‐reperfusion injury, which can result in systemic inflammation, multiorgan failure (particularly liver failure) and high mortality. Hinokitiol, a bioactive tropolone‐related compound, exhibits antiplatelet and anti‐inflammatory activities. Targeting inflammatory responses is a potential strategy for ameliorating hepatic injury during HS/R. Whether hinokitiol prevents hepatic injury during HS/R remains unclear. In the present study, we determined the role of hinokitiol following HS/R. The in vivo assays revealed that hinokitiol markedly attenuated HS/R‐induced hepatic injury. Hinokitiol could inhibited NF‐κB activation and IL‐6 and TNF‐α upregulation in liver tissues. Moreover, hinokitiol reduced caspase‐3 activation, upregulated Bax and downregulated Bcl‐2. These findings suggest that hinokitiol can ameliorate liver injury following HS/R, partly through suppression of inflammation and apoptosis. Furthermore, the in vitro data revealed that hinokitiol significantly reversed hypoxia/reoxygenation (H/R)‐induced cell death and apoptosis in the primary hepatocytes. Hinokitiol prevented H/R‐induced caspase‐3 activation, PPAR cleavage, Bax overexpression and Bcl‐2 downregulation. Moreover, hinokitiol attenuated H/R‐stimulated NF‐κB activation and reduced the levels of IL‐6 and TNF‐α mRNAs, suggesting that hinokitiol can protect hepatocytes from H/R injury. Collectively, our data suggest that hinokitiol attenuates liver injury following HS/R, partly through the inhibition of NF‐κB activation. 相似文献
110.
The implementation of the consensus on the management of Helicobacter pylori and barriers to consensus 下载免费PDF全文
Hsiu‐Chi Cheng Jyh‐Ming Liou Jiing‐Chyuan Luo Cheng‐Tang Chiu Ming‐Shiang Wu Yi‐Chia Lee Chun‐Ying Wu Deng‐Chyang Wu Ping‐I Hsu Chun‐Chao Chang Wei‐Lun Chang Jaw‐Town Lin Bor‐Shyang Sheu 《Helicobacter》2018,23(5)