全文获取类型
收费全文 | 298篇 |
免费 | 23篇 |
出版年
2023年 | 1篇 |
2022年 | 5篇 |
2021年 | 10篇 |
2020年 | 4篇 |
2019年 | 6篇 |
2018年 | 5篇 |
2017年 | 7篇 |
2016年 | 8篇 |
2015年 | 11篇 |
2014年 | 7篇 |
2013年 | 29篇 |
2012年 | 20篇 |
2011年 | 10篇 |
2010年 | 10篇 |
2009年 | 10篇 |
2008年 | 12篇 |
2007年 | 10篇 |
2006年 | 13篇 |
2005年 | 12篇 |
2004年 | 10篇 |
2003年 | 15篇 |
2002年 | 5篇 |
2001年 | 8篇 |
2000年 | 9篇 |
1999年 | 6篇 |
1998年 | 2篇 |
1997年 | 2篇 |
1996年 | 4篇 |
1995年 | 4篇 |
1994年 | 4篇 |
1993年 | 2篇 |
1992年 | 4篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 5篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1985年 | 6篇 |
1984年 | 11篇 |
1983年 | 6篇 |
1982年 | 4篇 |
1981年 | 1篇 |
1979年 | 5篇 |
1976年 | 1篇 |
1972年 | 1篇 |
1967年 | 4篇 |
1965年 | 1篇 |
排序方式: 共有321条查询结果,搜索用时 547 毫秒
101.
Effect of piperine,the active ingredient of black pepper,on intestinal secretion in mice 总被引:2,自引:0,他引:2
Capasso R Izzo AA Borrelli F Russo A Sautebin L Pinto A Capasso F Mascolo N 《Life sciences》2002,71(19):2311-2317
We have investigated the effect piperine on castor oil-stimulated fluid accumulation in the mouse small intestine. Piperine (2.5-20 mg/kg, i.p.) dose-dependently reduced castor oil-induced intestinal fluid accumulation. The inhibitory effect of piperine (10 mg/kg i.p.) was strongly attenuated in capsaicin (75 mg/kg in total, s.c.)-treated mice but it was not modified by the vanilloid receptor antagonist capsazepine (30 mg/kg i.p.). Pretreatment of mice with hexamethonium (1 mg/kg i.p.), naloxone (2 mg/kg i.p.), yohimbine (1 mg/kg i.p.) or the cannabinoid CB(1) receptor antagonist SR141716A (0.3 mg/kg i.p.) did not modify the inhibitory effect of piperine (10 mg/kg i.p.). These results suggest that piperine reduces castor oil-induced fluid secretion with a mechanism involving capsaicin-sensitive neurons, but not capsazepine-sensitive vanilloid receptors. 相似文献
102.
A Capasso E Parisi P De Prisco B De Petrocellis 《Cell biology international reports》1987,11(6):457-463
The role of neurotransmitters in sea-urchin eggs was investigated by studying their effect on adenylate cyclase of the egg membrane. Maximal stimulation of enzyme activity occurs in the presence of dopamine and GTP. 5-hydroxytriptamine, 5-methoxytriptamine and acetylcholine have no effect on activity, despite a decrease in intracellular cAMP level in eggs treated with 5-hydroxytriptamine antagonists as previously reported (Renaud et al., 1983). High-performance liquid chromatography (HPLC) revealed that dopamine is released from the sea-urchin egg into the external medium following fertilization. 相似文献
103.
Mohamed Bejaoui Eirini Pantazi Viviana De Luca Arnau Panisello Emma Folch-Puy Georgina Hotter Clemente Capasso Claudiu T. Supuran Joan Rosselló-Catafau 《PloS one》2015,10(7)
Carbonic anhydrases (CAs) are ubiquitous metalloenzymes that catalyze the reversible hydration of carbon dioxide to bicarbonate and a proton. CAs are involved in numerous physiological and pathological processes, including acid-base homeostasis, electrolyte balance, oxygen delivery to tissues and nitric oxide generation. Given that these processes are found to be dysregulated during ischemia reperfusion injury (IRI), and taking into account the high vulnerability of steatotic livers to preservation injury, we hypothesized a new role for CA as a pharmacological agent able to protect against ischemic damage. Two different aspects of the role of CA II in fatty liver grafts preservation were evaluated: 1) the effect of its addition to Institut Georges Lopez (IGL-1) storage solution after cold ischemia; 2) and after 24h of cold storage followed by two hours of normothermic ex-vivo perfusion. In all cases, liver injury, CA II protein concentration, CA II mRNA levels and CA II activity were determined. In case of the ex-vivo perfusion, we further assessed liver function (bile production, bromosulfophthalein clearance) and Western blot analysis of phosphorylated adenosine monophosphate activated protein kinase (AMPK), mitogen activated protein kinases family (MAPKs) and endoplasmic reticulum stress (ERS) parameters (GRP78, PERK, IRE, eIF2α and ATF6). We found that CA II was downregulated after cold ischemia. The addition of bovine CA II to IGL-1 preservation solution efficiently protected steatotic liver against cold IRI. In the case of reperfusion, CA II protection was associated with better function, AMPK activation and the prevention of ERS and MAPKs activation. Interestingly, CA II supplementation was not associated with enhanced CO2 hydration. The results suggest that CA II modulation may be a promising target for fatty liver graft preservation. 相似文献
104.
The Protective Effect of Apocynin on Cyclosporine A‐Induced Hypertension and Nephrotoxicity in Rats 下载免费PDF全文
105.
Siham A. Alissa Hanan A. Alghulikah Zeid A. ALOthman Sameh M. Osman Sonia Del Prete Clemente Capasso 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):377-382
Abstract The inhibition of δ- and η-class carbonic anhydrases (CAs; EC 4.2.1.1) was poorly investigated so far. Only one δ-CA, TweCA from the diatom Thalassiosira weissflogii, and one η-CA, PfCA, from Plasmodium falciparum, have been cloned and characterised to date. To enrich δ- and η-CAs inhibition profiles, a panel of 22 phenols was investigated for TweCA and PfCA inhibition. Some derivatives showed effective, sub-micromolar inhibition of TweCA (KIs 0.81–65.4?µM) and PfCA (KIs 0.62–78.7?µM). A subset of compounds demonstrated a significant selectivity for the target CAs over the human physiologically relevant ones. This study promotes the identification of new potent and selective inhibitors of TweCA and PfCA, which could be considered as leads for finding molecular probes in the study of carbon fixation processes (in which TweCA and orthologue enzymes are involved) or drug candidates in the treatment of malaria. 相似文献
106.
107.
Immacolata Andolfo Vito A. Lasorsa Francesco Manna Barbara E. Rosato Daniela Formicola Achille Iolascon Mario Capasso 《Journal of cellular and molecular medicine》2020,24(11):6459-6471
Neuroblastoma (NB) is the most common extracranial neoplasm in children. The overall outcome for high-risk NB patients is still unacceptable, therefore, it is critical to deeply understand molecular mechanisms associated with NB, which in turn can be utilized for developing drugs towards the treatment of NB. Protein kinases (TKs) play an essential role in the regulation of cell survival and proliferation. Different kinases, such as anaplastic lymphoma kinase (ALK), Aurora kinase, RET receptor tyrosine kinase, are potential therapeutic targets in various cancers, including NB. We analysed a cohort of 45 high-risk NB patients and 9 NB cell lines by a targeted—(t)NGS custom gene panel (genes codifying for the kinase domains of 90 TKs). We identified somatic variants in four TK genes (ALK, EPHB4, LMTK3 and EPHB6) in NB patients and we functionally characterized an interesting somatic variant, V871I, in EPHB4 gene. EPHB4 plays a crucial role in cardiovascular development and regulates vascularization in cancer-promoting angiogenesis, tumour growth and metastasis. Several EPHB4 mutations have previously been identified in solid and haematological tumour specimens but EPHB4 mutations were not described until now in NB. Interestingly, a re-analysis of public CGH-array showed that the EPHB4 gain is associated with advanced diseases in NB. We further demonstrated that higher EPHB4 expression is correlated to stage 4 of NB and with poor overall survival. Additionally, we also revealed that the EPHB4-V871I accounts for increased proliferation, migration and invasion properties in two NB cell lines by acting on VEGF, c-RAF and CDK4 target genes and by increasing the phosphorylation of ERK1-2 pathway. The use of two EPHB4 inhibitors, JI-101 and NVP-BHG712, was able to rescue the phenotype driven by the variant. Our study suggested that EPHB4 is a promising therapeutic target in high-risk NB. 相似文献
108.
109.
Daniela Vullo R. Siva Sai Kumar Andrea Scozzafava Clemente Capasso James G. Ferry Claudiu T. Supuran 《Bioorganic & medicinal chemistry letters》2013,23(24):6706-6710
A β-carbonic anhydrases (CAs, EC 4.2.1.1) was recently cloned, purified and characterized kinetically in the pathogen Clostridium perfringens. We report here the first inhibition study of this enzyme (CpeCA). CpeCA was poorly inhibited by iodide and bromide, and was inhibited with KIs in the range of 1–10 mM by a range of anions such as (thio)cyanate, azide, bicarbonate, nitrate, nitrite, hydrogensulfite, hydrogensulfide, stannate, tellurate, pyrophosphate, divanadate, tetraborate, peroxydisulfate, sulfate, iminodisulfonate and fluorosulfonate. Better inhibitory power, with KIs of 0.36–1.0 mM, was observed for cyanide, carbonate, selenate, selenocyanide, trithiocarbonate and diethyldithiocarbamate, whereas the best CpeCA inhibitors were sulfamate, sulfamide, phenylboronic acid and phenylarsonic acid, which had KIs in the range of 7–75 μM. This study thus provides the basis for developing better clostridial enzyme inhibitors with potential as antiinfectives with a new mechanism of action. 相似文献
110.
Daniela Vullo Semra Isik Sonia Del Prete Viviana De Luca Vincenzo Carginale Andrea Scozzafava Claudiu T. Supuran Clemente Capasso 《Bioorganic & medicinal chemistry letters》2013,23(6):1636-1638
An α-carbonic anhydrase (CA, EC 4.2.1.1) has been recently cloned and characterized in the human pathogenic bacterium Vibrio cholerae, denominated VchCA (Del Prete et al. J. Med. Chem. 2012, 55, 10742). This enzyme shows a good catalytic activity for the CO2 hydration reaction, comparable to that of the human (h) isoform hCA I. Many inorganic anions and several small molecules were investigated as VchCA inhibitors. Inorganic anions such as cyanate, cyanide, hydrogen sulfide, hydrogen sulfite, and trithiocarbonate were effective VchCA inhibitors with inhibition constants in the range of 33–88 μM. Other effective inhibitors were diethyldithiocarbamate, sulfamide, sulfamate, phenylboronic acid and phenylarsonic acid, with KIs of 7–43 μM. Halides (bromide, iodide), bicarbonate and carbonate were much less effective VchCA inhibitors, with KIs in the range of 4.64–28.0 mM. The resistance of VchCA to bicarbonate inhibition may represent an evolutionary adaptation of this enzyme to living in an environment rich in this ion, such as the gastrointestinal tract, as bicarbonate is a virulence enhancer of this bacterium. 相似文献