全文获取类型
收费全文 | 297篇 |
免费 | 15篇 |
国内免费 | 1篇 |
出版年
2024年 | 1篇 |
2022年 | 4篇 |
2021年 | 9篇 |
2019年 | 12篇 |
2018年 | 10篇 |
2017年 | 5篇 |
2016年 | 15篇 |
2015年 | 19篇 |
2014年 | 21篇 |
2013年 | 37篇 |
2012年 | 28篇 |
2011年 | 17篇 |
2010年 | 16篇 |
2009年 | 13篇 |
2008年 | 18篇 |
2007年 | 12篇 |
2006年 | 16篇 |
2005年 | 14篇 |
2004年 | 8篇 |
2003年 | 8篇 |
2002年 | 3篇 |
2001年 | 4篇 |
2000年 | 1篇 |
1999年 | 3篇 |
1998年 | 2篇 |
1997年 | 1篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1989年 | 2篇 |
1986年 | 1篇 |
1984年 | 1篇 |
1982年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1971年 | 1篇 |
1968年 | 1篇 |
排序方式: 共有313条查询结果,搜索用时 843 毫秒
51.
Thiosemicarbazones (1-7) and their palladium(II) complexes (1a-7a) of the type [Pd(TSCN)Cl(2)] (where TSCN=thiosemicarbazone) were prepared from 5-nitro thiophene-2-carboxaldehyde and [Pd(DMSO)(2)Cl(2)], respectively. Coordination via the thionic sulphur and the azomethine nitrogen atom of the thiosemicarbazones to the metal ion were confirmed by spectral data. These compounds were screened in vitro against (HK-9) strain of Entamoeba histolytica possess amoebicidal properties. Enhancement of antiamoebic activity resulted due to the introduction of palladium metal in the thiosemicarbazone moiety. The most promising of the group tested are [Pd(5-N-2-TCA-COTSCN)Cl(2)] and [Pd(5-N-2-TCA-AdmTSCN)Cl(2)] comparable to that of metronidazole. 相似文献
52.
We report here the synthesis, characterization and in vitro antiamoebic activity of 5-nitrothiophene-2-carboxaldehyde thiosemicarbazones (TSC), 1–5, and their bidentate complexes [Ru(η4-C8H12)(TSC)Cl2] 1a–5a. The biological studies of these compounds were investigated against HK-9 strain of Entamoeba histolytica and the concentration causing 50% cell growth inhibition (IC50) was calculated in the micromolar range. The ligands exhibited antiamoebic activity in the range (2.05–5.29 μM). Screening results indicated that the potencies of the compounds increased by the incorporation of ruthenium(II) in the thiosemicarbazones. The complexes 1a–5a showed antiamoebic activity with an IC50 of 0.61–1.43 μM and were better inhibitors of growth of E. histolytica, based on IC50 values. The most promising among them is Ru(II) complex 2a having 1,2,3,4-tetrahydroquinoline as N4 substitution. 相似文献
53.
Preet Kamal Kaur Neha Tripathi Jayesh Desale Soumya Neelagiri Shailendra Yadav Prasad V. Bharatam Sushma Singh 《PloS one》2016,11(3)
Ribose-5-phosphate isomerase B from Leishmania donovani (LdRpiB) is one of the potential drug targets against visceral leishmaniasis. In the present study, we have targeted several conserved amino acids for mutational analysis (i.e. Cys69, His11, His102, His138, Asp45, Tyr46, Pro47 and Glu149) to gain crucial insights into their role in substrate binding, catalysis and conformational stability of the enzyme. All the eight LdRpiB variants were cloned, sequenced, expressed and purified. C69S, H102N, D45N and E149A mutants exhibited complete loss of enzyme activity indicating that they are indispensable for the enzyme activity. Kinetic parameters were altered in case of H138N, H11N and P47A variants; however Y46F exhibited similar kinetic behaviour as wild type. All the mutants except H138N exhibited altered protein structure as determined by CD and fluorescence spectral analysis. This data was supported by the atomic level details of the conformational changes and substrate binding using molecular dynamic simulations. LdRpiB also exhibited activity with D-form of various aldose substrates in the order of D-ribose > D-talose > D-allose > D-arabinose. Our study provides insights for better understanding of substrate enzyme interactions which can rationalize the process of drug design against parasite RpiB. 相似文献
54.
55.
56.
57.
5‐Aminoimidazole‐4‐carboxamide ribonucleoside‐mediated adenosine monophosphate‐activated protein kinase activation induces protective innate responses in bacterial endophthalmitis
下载免费PDF全文
![点击此处可从《Cellular microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
The retina is considered to be the most metabolically active tissue in the body. However, the link between energy metabolism and retinal inflammation, as incited by microbial infection such as endophthalmitis, remains unexplored. In this study, using a mouse model of Staphylococcus aureus (SA) endophthalmitis, we demonstrate that the activity (phosphorylation) of 5' adenosine monophosphate‐activated protein kinase alpha (AMPKα), a cellular energy sensor and its endogenous substrate; acetyl‐CoA carboxylase is down‐regulated in the SA‐infected retina. Intravitreal administration of an AMPK activator, 5‐aminoimidazole‐4‐carboxamide ribonucleoside (AICAR), restored AMPKα and acetyl‐CoA carboxylase phosphorylation. AICAR treatment reduced both the bacterial burden and intraocular inflammation in SA‐infected eyes by inhibiting NF‐kB and MAP kinases (p38 and JNK) signalling. The anti‐inflammatory effects of AICAR were diminished in eyes pretreated with AMPK inhibitor, Compound C. The bioenergetics (Seahorse) analysis of SA‐infected microglia and bone marrow‐derived macrophages revealed an increase in glycolysis, which was reinstated by AICAR treatment. AICAR also reduced the expression of SA‐induced glycolytic genes, including hexokinase 2 and glucose transporter 1 in microglia, bone marrow‐derived macrophages and the mouse retina. Interestingly, AICAR treatment enhanced the bacterial phagocytic and intracellular killing activities of cultured microglia, macrophages and neutrophils. Furthermore, AMPKα1 global knockout mice exhibited increased susceptibility towards SA endophthalmitis, as evidenced by increased inflammatory mediators and bacterial burden and reduced retinal function. Together, these findings provide the first evidence that AMPK activation promotes retinal innate defence in endophthalmitis by modulating energy metabolism and that it can be targeted therapeutically to treat ocular infections. 相似文献
58.
Vineet Kumar Srivastava Shailendra Raikwar Renu Tuteja Narendra Tuteja 《Plant cell reports》2016,35(5):1021-1041
Key message
PsSEOF-1 binds to calcium and its expression is upregulated by salinity treatment. PsSEOF - 1 -overexpressing transgenic tobacco showed enhanced salinity stress tolerance by maintaining cellular ion homeostasis and modulating ROS-scavenging pathway.Abstract
Calcium (Ca2+) plays important role in growth, development and stress tolerance in plants. Cellular Ca2+ homeostasis is achieved by the collective action of channels, pumps, antiporters and by Ca2+ chelators present in the cell like calcium-binding proteins. Forisomes are ATP-independent mechanically active motor proteins known to function in wound sealing of injured sieve elements of phloem tissue. The Ca2+-binding activity of forisome and its role in abiotic stress signaling were largely unknown. Here we report the Ca2+-binding activity of pea forisome (PsSEO-F1) and its novel function in promoting salinity tolerance in transgenic tobacco. Native PsSEO-F1 promoter positively responded in salinity stress as confirmed using GUS reporter. Overexpression of PsSEO-F1 tobacco plants confers salinity tolerance by alleviating ionic toxicity and increased ROS scavenging activity which probably results in reduced membrane damage and improved yield under salinity stress. Evaluation of several physiological indices shows an increase in relative water content, electrolyte leakage, proline accumulation and chlorophyll content in transgenic lines as compared with null-segregant control. Expression of several genes involved in cellular homeostasis is perturbed by PsSEO-F1 overexpression. These findings suggest that PsSEO-F1 provides salinity tolerance through cellular Ca2+ homeostasis which in turn modulates ROS machinery providing indirect link between Ca2+ and ROS signaling under salinity-induced perturbation. PsSEO-F1 most likely functions in salinity stress tolerance by improving antioxidant machinery and mitigating ion toxicity in transgenic lines. This finding should make an important contribution in our better understanding of the significance of calcium signaling in phloem tissue leading to salinity stress tolerance.59.
Rajesh P. Rastogi Shailendra P. Singh Rajeshwar P. Sinha 《Biochemical and biophysical research communications》2010,397(3):603-607
The generation of reactive oxygen species (ROS) under simulated solar radiation (UV-B: 0.30 Wm−2, UV-A: 25.70 Wm−2 and PAR: 118.06 Wm−2) was studied in the cyanobacterium Anabaena variabilis PCC 7937 using the oxidant-sensing fluorescent probe 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA). DCFH-DA is a nonpolar dye, converted into the polar derivative DCFH by cellular esterases that are nonfluorescent but switched to highly fluorescent DCF when oxidized by intracellular ROS and other peroxides. The images obtained from the fluorescence microscope after 12 h of irradiation showed green fluorescence from cells covered with 295, 320 or 395 nm cut-off filters, indicating the generation of ROS in all treatments. However, the green/red fluorescence ratio obtained from fluorescence microscopic analysis showed the highest generation of ROS after UV-B radiation in comparison to PAR or UV-A radiation. Production of ROS was also measured by a spectrofluorophotometer and results obtained supported the results of fluorescence microscopy. Low levels of ROS were detected at the start (0 h) of the experiment showing that they are generated even during normal metabolism. This study also showed that UV-B radiation causes the fragmentation of the cyanobacterial filaments which could be due to the observed oxidative stress. This is the first report for the detection of intracellular ROS in a cyanobacterium by fluorescence microscopy using DCFH-DA and thereby suggesting the applicability of this method in the study of in vivo generation of ROS. 相似文献
60.