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71.
The cholinergic anti-inflammatory pathway is one of the putative biochemical pathways that link diabetes with Alzheimer disease. Hence, we aimed to verify the potential antidiabetic effect of galantamine, unveil the possible mechanisms and evaluate its interaction with vildagliptin. The n5-STZ rat model was adopted and the diabetic animals were treated with galantamine and/or vildagliptin for 4 weeks. Galantamine lowered the n5-STZ-induced elevation in body weight, food/water intake, serum levels of glucose, fructosamine, and ALT/AST, as well as AChE in the tested organs. Moreover, it modulated successfully the lipid profile assessed in serum, liver, and muscle, and increased serum insulin level, as well as % β-cell function, in a pattern similar to that of vildagliptin. Additionally, galantamine confirmed its antioxidant (Nrf2, TAC, MDA), anti-inflammatory (NF-κB, TNF-α, visfatin, adiponectin) and anti-apoptotic (caspase-3, cytochrome c) capabilities by altering the n5-STZ effect on all the aforementioned parameters. On the molecular level, galantamine/vildagliptin have improved the insulin (p-insulin receptor, p-Akt, GLUT4/GLUT2) and Wnt/β-catenin (p-GSK-3β, β-catenin) signaling pathways. On almost all parameters, the galantamine effects surpassed that of vildagliptin, while the combination regimen showed the best effects. The present results clearly proved that galantamine modulated glucose/lipid profile possibly through its anti-oxidant, -apoptotic, -inflammatory and -cholinesterase properties. These effects could be attributed partly to the enhancement of insulin and Wnt/β-catenin signaling pathways. Galantamine can be strongly considered as a potential antidiabetic agent and as an add-on therapy with other oral antidiabetics. 相似文献
72.
Prophylactic administration of carnosine and melatonin abates the incidence of renal toxicity induced by an over dose of titanium dioxide nanoparticles 下载免费PDF全文
Laila Mohamed Fadda Azza M. Mohamed Hanaa Mahmoud Ali Hanan Hagar Manal Aldossari 《Journal of biochemical and molecular toxicology》2018,32(3)
The alleviative effects of two antioxidants, carnosine (Car) and melatonin (Mel), against titanium dioxide nanoparticles (TiO2‐NPs) toxicity‐induced oxidative and inflammatory renal damage were examined in rats. Administration of these antioxidants along with TiO2‐NPs effectively reduced serum urea, uric acid, creatinine, glucose, tumor necrosis factor‐α, interleukin‐6, C‐reactive protein, immunoglobulin G, vascular endothelial growth factor, and nitric oxide, as well as a significant amelioration of the decrease in glutathione levels in renal tissue was observed, compared to those in rats treated with TiO2‐NPs alone. The renoprotective properties of the antioxidants were confirmed by reduced intensity of renal damage as demonstrated by histological findings. In conclusion, Car and Mel play protective roles against TiO2‐NPs‐induced renal inflammation and oxidative injury, likely due to their antioxidant and anti‐inflammatory properties. 相似文献
73.
Lucie Gueneau Richard J. Fish Hanan E. Shamseldin Norine Voisin Frédéric Tran Mau-Them Egle Preiksaitiene Glen R. Monroe Angeline Lai Audrey Putoux Fabienne Allias Qamariya Ambusaidi Laima Ambrozaityte Loreta Cimbalistienė Julien Delafontaine Nicolas Guex Mais Hashem Wesam Kurdi Saumya Shekhar Jamuar Alexandre Reymond 《American journal of human genetics》2018,102(1):116-132
74.
The plant-derived sesquiterpene lactone parthenolide (PTL) was recently found to possess promising anticancer activity but elaboration of this natural product scaffold for optimization of its pharmacological properties has proven challenging via available chemical methods. In this work, P450-catalyzed C–H hydroxylation of positions C9 and C14 in PTL was coupled to carbamoylation chemistry to yield a panel of novel carbamate-based PTL analogs (‘parthenologs’). These compounds, along with a series of other C9- and C14-functionalized parthenologs obtained via O–H acylation, alkylation, and metal-catalyzed carbene insertion, were profiled for their cytotoxicity against a diverse panel of human cancer cell lines. These studies led to the discovery of several parthenologs with significantly improved anticancer activity (2–14-fold) compared to the parent molecule. Most interestingly, two PTL analogs with high cytotoxicity (LC50 ~ 1–3 μM) against T cell leukemia (Jurkat), mantle cell lymphoma (JeKo-1), and adenocarcinoma (HeLa) cells as well as a carbamate derivative with potent activity (LC50 = 0.6 μM) against neuroblastoma cells (SK-N-MC) were obtained. In addition, these analyses resulted in the identification of parthenologs featuring both a broad spectrum and tumor cell-specific anticancer activity profile, thus providing valuable probes for the future investigation of biomolecular targets that can affect cell viability across multiple as well as specific types of human cancers. Altogether, these results highlight the potential of P450-mediated chemoenzymatic C–H functionalization toward tuning and improving the anticancer activity of the natural product parthenolide. 相似文献
75.
Blair M. Goodridge Erin J. Hanan Rosana Aguilera Erin B. Wetherley Ying-Jung Chen Carla M. D’Antonio John M. Melack 《Ecosystems》2018,21(8):1608-1622
Wildfires alter nitrogen (N) cycling in Mediterranean-type ecosystems, resetting plant and soil microbial growth, combusting plant biomass to ash, and enhancing N availability in the upper soil layer. This ash and soil N pool (that is, wildfire N) is susceptible to loss from watersheds via runoff and leaching during post-fire rains. Plant and soil microbial recovery may mitigate these losses by sequestering N compounds in new biomass, thereby promoting landscape N retention in N-limited chaparral ecosystems. We investigated the relative balance between wildfire N loss, and plant and soil microbial N uptake and stream N export for an upland chaparral watershed in southern California that burned (61%) in a high-intensity wildfire in 2009 by using a combination of stream, vegetation, soil microbial, and remote sensing analyses. Soil N in the burn scar was 440% higher than unburned soil N in the beginning of the first post-fire wet season and returned within 66 days to pre-fire levels. Stream N export was 1480% higher than pre-fire export during the first post-fire rain and returned within 106 days over the course of the following three rainstorms to pre-fire levels. A watershed-scale N mass balance revealed that 52% of wildfire N could be accounted for in plant and soil microbial growth, whereas 1% could be accounted for in stream export of dissolved nitrogen. 相似文献
76.
All published records for the 49 species of moth flies known from North Africa are reviewed and discussed: Morocco (27 species), Algeria (33 species), Tunisia (18 species) and Egypt (five species). In addition, records of seven species of Psychodinae new to the fauna of Morocco are added, of which three are new mentions for North Africa (Table (Table1)1) and one is a new record for Egypt. Telmatoscopus
squamifer Tonnoir, 1922 is transferred to the genus Iranotelmatoscopus Ježek, 1987, comb. n. Satchelliella
reghayana Boumezzough & Vaillant, 1987 is transferred to the genus Pneumia Enderlein, 1935, comb. n. Pneumia
aberrans Tonnoir, 1922 is transferred to the subgenus Logima.
Open in a separate windowX***: new species for North Africa; X**: new species for Morocco or Egypt; X*: new species for the Rif Mountains. 相似文献
Table 1.
Species (in alphabetical order) of Psychodinae known from the North African countries. Libya has been omitted because no information exists in the literature from Libya.Morocco | Algeria | Tunisia | Egypt | |
---|---|---|---|---|
Bazarella atra (Vaillant, 1955) | X* | X | ||
Berdeniella lucasii (Satchell, 1955) | X | |||
Clogmia albipunctata (Williston, 1893) | X** | X | X | |
Clytocerus kabylicus Wagner, 1987 | X | |||
Iranotelmatoscopus numidicus (Satchell, 1955) | X | |||
Iranotelmatoscopus squamifer (Tonnoir, 1922) | X | |||
Lepiseodina tristis (Meigen, 1830) | X | |||
Mormia tenebricosa (Vaillant, 1954) | X* | X | X | |
Mormia riparia (Satchell, 1955) | X | |||
Mormia similis Wagner, 1987 | X | |||
Panimerus goetghebueri (Tonnoir, 1919) | X | X | ||
Panimerus thienemanni (Vaillant, 1954) | X | X | X | |
Paramormia ustulata (Walker, 1856) | X* | X | X | |
Pericoma barbarica Vaillant, 1955 | X* | X | X | |
Pericoma blandula Eaton, 1893 | X | X | X | |
Pericoma diversa Tonnoir, 1920 | X* | |||
Pericoma exquisita Eaton, 1893 | X | X | X | |
Pericoma granadica Vaillant, 1978 | X* | |||
Pericoma latina Sarà, 1954 | X* | X | ||
Pericoma maroccana Vaillant, 1955 | X* | |||
Pericoma modesta Tonnoir, 1922 | X | X | ||
Pericoma pseudexquisita Tonnoir, 1940 | X*** | |||
Philosepedon beaucournui Vaillant, 1974 | X | X | ||
Philosepedon humerale (Meigen, 1818) | X** | X | ||
Pneumia nubila (Meigen, 1818) | X*** | |||
Pneumia pilularia (Tonnoir, 1940) | X | X | ||
Pneumia propinqua (Satchell, 1955) | X** | X | ||
Pneumia reghayana (Boumezzough & Vaillant, 1986) | X | |||
Pneumia toubkalensis (Omelková & Ježek 2012) | X* | |||
Psychoda aberrans Tonnoir, 1922 | X | |||
Psychoda (Falsologima) savaiiensis Edwards, 1928 | X | |||
Psychoda (Logima) albipennis Zetterstedt, 1850 | X | X | ||
Psychoda (Logima) erminea Eaton, 1893 | X | |||
Psychoda (Psycha) grisescens Tonnoir, 1922 | X | X | X | |
Psychoda (Psychoda) phalaenoides (Linnaeus, 1758) | X | |||
Psychoda (Psychoda) uniformata Haseman, 1907 | X | |||
Psychoda (Psychodocha) cinerea Banks, 1894 | X** | X | X | |
Psychoda (Psychodocha) gemina (Eaton, 1904) | X*** | |||
Psychoda (Psychomora) trinodulosa Tonnoir, 1922 | X | |||
Psychoda (Tinearia) alternata Say, 1824 | X* | X | X | X** |
Psychoda (Tinearia) efflatouni Tonnoir, 1922 | X | |||
Psychoda (Tinearia) lativentris Berden, 1952 | X | |||
Telmatoscopus advena (Eaton, 1893) | X | |||
Thornburghiella quezeli (Vaillant, 1955) | X | X | ||
Tonnoiriella atlantica (Satchell, 1953) | X | X | ||
Tonnoiriella paveli Ježek, 1999 | X | |||
Tonnoiriella pulchra (Eaton, 1893) | X | X | ||
Vaillantodes fraudulentus (Eaton, 1896) | X | X | ||
Vaillantodes malickyi (Wagner, 1987) | X |
77.
Wissam H. Faour Mohamed Mroueh Costatantine F. Daher Hanan M. Ragab Asser I. Ghoneim 《Journal of enzyme inhibition and medicinal chemistry》2016,31(6):1079-1094
Four series of new bipyrazoles comprising the N-phenylpyrazole scaffold linked to polysubstituted pyrazoles or to antipyrine moiety through different amide linkages were synthesized. The synthesized compounds were evaluated for their anti-inflammatory and analgesic activities. In vitro COX-1/COX-2 inhibition study revealed that compound 16b possessed the lowest IC50 value against both COX-1 and COX-2. Moreover, the effect of the most promising compounds on inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) protein expression in lipopolysaccharide (LPS)-activated rat monocytes was also investigated. The results revealed that some of the synthesized compounds showed anti-inflammatory and/or analgesic activity with less ulcerogenic potential than the reference drug diclofenac sodium and are well tolerated by experimental animals. Moreover, they significantly inhibited iNOS and COX-2 protein expression induced by LPS stimulation. Compounds 16b and 18 were proved to display anti-inflammatory activity superior to diclofenac sodium and analgesic activity equivalent to it with minimal ulcerogenic potential. 相似文献
78.
Hanan E. Shamseldin Abdulrahman Aldeeri Zainab Babay Abdulrahman Alsultan Mais Hashem Fowzan S. Alkuraya 《Human genetics》2016,135(10):1209-1211
The role of plasminogen in preventing thrombosis requires activation by tissue plasminogen activator (t-PA) encoded by PLAT. While case–control associations have been pursued for common variants in PLAT, no disease-causing mutations have been reported. We describe a consanguineous family with two children who died shortly after birth due to complications related to severe hydranencephaly and diaphragmatic hernia. A combined exome/autozygome analysis was carried out with informed consent. We identified a homozygous null mutation in PLAT that abrogated t-PA level in patient cells. This is the first reported human knockout mutation of PLAT. The apparent association with hydranencephaly, diaphragmatic hernia and postnatal lethality requires further validation. 相似文献
79.
80.
BackgroundEgypt has the highest prevalence of a difficult to treat chronic hepatitis C virus (HCV), genotype 4. Pretreatment factors could guide individualization of therapy which aids in treatment optimization and interleukin IL28B gene polymorphism has been shown to closely relate to HCV treatment response. Polymorphisms in genes encoding inhibitors of T-cell response, which have role in disease progression as Programmed Cell Death 1 (PD-1), and Cytotoxic T-Lymphocytes Antigen-4 (CTLA-4), could be candidate markers predicting treatment response.MethodsThis cohort study consisted of 200 chronic HCV genotype 4 infected patients treated with PegIFN α-2a and RBV in 2 hepatology centers. Genotyping of the polymorphisms in the IL28B gene region (rs12979860), PD1.3 (rs11568821) and CTLA-4 (rs231775) was performed on DNA collected from each patient using TaqMan® genotyping assay. Groups were classified according to response into sustained virological responders (SVR), or non-responders (NR). A multivariate logistic regression analysis was used to identify potential markers, host pretreatment clinical and viral predictive factors including viral load, insulin resistance, and alpha fetoprotein (AFP) related to treatment response.ResultsOur results showed that in a multivariate analyses IL28B C/C genotype was the most significant predictor for SVR (OR = 10.86; p<0.0001) followed by AFP (OR = 0.915; p = 0.001) then CTLA-4/G genotypes (OR = 1.948; p = 0.022). However, PD-1.3/A genotypes and platelets count were significantly related to response in univariate analysis only (OR = 1.973; p = 0.023; OR = 1.007; p = 0.009 respectively).ConclusionIL28B SNP, AFP level, and CTLA-4 SNP could be used in conjunction to predict treatment response in HCV genotype 4 infected Egyptian patients. 相似文献