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41.
Ali Nasrollahzadeh Majid Momeny Hamidreza Fasehee Marjan Yaghmaie Davood Bashash Saeed Hassani Seyed A. Mousavi Seyed H. Ghaffari 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2021,1868(10):119087
Due to its potent anti-tumor activity, well-investigated pharmacokinetic properties and safety profile, disulfiram (DSF) has emerged as a promising candidate for drug repurposing in cancer therapy. Although several molecular mechanisms have been proposed for its anti-cancer effects, the precise underlying mechanisms remain unclear. In the present study, we showed that DSF inhibited proliferation of cancer cells by inducing reactive oxygen species (ROS) production, a G1 cell cycle arrest and autophagy. Moreover, DSF triggered apoptosis via suppression of the anti-apoptotic protein survivin.To elucidate the mechanisms for the anti-proliferative activities of DSF, we applied a 2-DE combined with MALDI-TOF-MS/MS analysis to identify differentially expressed proteins in breast cancer cells upon treatment with DSF. Nine differentially expressed proteins were identified among which, three candidates including calmodulin (CaM), peroxiredoxin 1 (PRDX1) and collagen type I alpha 1 (COL1A1) are involved in the regulation of the AKT signaling pathway. The results of western blot analysis confirmed that DSF inhibited p-AKT, suggesting that DSF induces its anti-tumor effects via AKT blockade. Moreover, we found that DSF increased the mRNA levels of FOXO1, FOXO3 and FOXO4, and upregulated the expression of their target genes involved in G1 cell cycle arrest, apoptosis and autophagy. Finally, DSF potentiated the anti-proliferative effects of well-known chemotherapeutic agents such as arsenic trioxide (ATO), doxorubicin, paclitaxel and cisplatin. Altogether, these findings provide mechanistic insights into the anti-growth activities of DSF. 相似文献
42.
Fatemeh Fotouhi Mostafa Salehi-Vaziri Behrokh Farahmand Ehsan Mostafavi Mohammad Hassan Pouriayevali Tahmineh Jalali Vahideh Mazaheri Mona Sadat Larijani Mahsa Tavakoli Azita Eshratkhah mohammadnejad Neda Afzali Afsaneh Zokaei SeyedeAtefe Hosseini Mohamad Mahdi Mortazavipour FaridehNiknam Oskouei Amitis Ramezani 《Microbes and infection / Institut Pasteur》2021,23(4-5):104810
SARS-CoV-2 as a new global threat has affected global population for one year. Despite the great effort to eradicate this infection, there are still some challenges including different viral presentation, temporal immunity in infected individuals and variable data of viral shedding. We studied 255 COVID-19 suspected individuals to assess the viral shedding duration and also the antibody development against SARS-CoV-2 among the cases. Real Time RT-PCR assay was applied to determine the virus presence and SARS-CoV-2 antibodies were evaluated using SARS-CoV-2 IgM and IgG kits. 113 patients were confirmed for COVID-19 infection. The patients were followed until negative PCR achieved. The median viral shedding among studied population was obtained 34.16 (±17.65) days which was not significantly associated with age, sex and underlying diseases. Shiver and body pain were found in prolonged form of the infection and also patients who had gastrointestinal problems experienced longer viral shedding. Moreover, IgG was present in 84% of patients after 150 days. According to this data, the median viral shedding prolongation was 34.16 days which indicates that 14 days isolation might not be enough for population. In addition, IgG profiling indicated that it is persistent in a majority of patients for nearly 6 months which has brought some hopes in vaccine efficacy and application. 相似文献
43.
Allelic frequency and genotypes of prion protein at codon 136 and 171 in Iranian Ghezel sheep breeds
Siamak Salami Reza Ashrafi Zadeh Mir Davood Omrani Fatemeh Ramezani Amir Amniattalab 《朊病毒》2011,5(3):228-231
PrP genotypes at codons 136 and 171 in 120 Iranian Ghezel sheep breeds were studied using allele-specific PCR amplification and compared with the well-known sheep breeds in North America, the United States and Europe. The frequency of V allele and VV genotype at codon 136 of Ghezel sheep breed was significantly lower than AA and AV. At codon 171, the frequency of allele H was significantly lower than Q and R. Despite the similarities of PrP genotypes at codons 136 and 171 between Iranian Ghezel sheep breeds and some of the studied breeds, significant differences were found with others. Planning of effective breeding control and successful eradication of susceptible genotypes in Iranian Ghezel sheep breeds will not be possible unless the susceptibility of various genotypes in Ghezel sheep breeds to natural or experimental scrapie has been elucidated.Key words: scrapie, Ghezel sheep breed, PrP genotyping, allele specific amplification, codon 136, codon 171Scrapie was first described in England in 1732,1 and it is an infectious neurodegenerative fatal disease of sheep and goats belonging to the group of transmissible subacute spongiform encephalopathies (TSEs), along with bovine spongiform encephalopathy (BSE), chronic wasting disease and Creutzfeldt-Jakob disease.2,3 The term prion, proteinaceous infectious particles, coined by Stanley B. Prusiner, was introduced, and he presents the idea that the causal agent is a protein.4 Prion proteins are discovered in two forms, the wild-type form (PrPc) and the mutant form (PrPSc).5 Although scrapie is an infectious disease, the susceptibility of sheep is influenced by genotypes of the prion protein (PrP) gene.2,6 Researchers have found that the PrP allelic variant alanine/arginine/arginine (ARR) at codons 136, 154 and 171 is associated with resistance to scrapie in several breeds.7–14 Most of the sheep populations in the Near East and North African Region (84% of the total population of 255 million) are raised in Iran, Turkey, Pakistan, Sudan, Algeria, Morocco, Afghanistan, Syria and Somalia.15 In 2003, the Iranian sheep population was estimated at 54,000,000 head. The Ghezel sheep breed, which also is known as Kizil-Karaman, Mor-Karaman, Dugli, Erzurum, Chacra, Chagra, Chakra, Gesel, Gezel, Kazil, Khezel, Khizel, Kizil, Qezel, Qizil and Turkish Brown, originated in northwestern Iran and northeastern Turkey. By considering sheep breeds as one of the main sources of meat, dairy products and related products, a global screening attempt is started in different areas. In compliance with European Union Decision 2003/100/EC, each member state has introduced a breeding program to select for resistance to TSEs in sheep populations to increase the frequency of the ARR allele. A similar breeding program is established in United States and Canada. The Near East and North African Region still needs additional programs to help the global plan of eradication of scrapie-susceptible genotypes. The current study was the first to assess the geographical and molecular variation of codons 136 and 171 polymorphism between Iranian Ghezel sheep breed and well-known sheep breeds.Polymorphism at codon 136 is associated with susceptibility to scrapie in both experimental and natural models.10,11,13,16 17 and Austrian Carynthian sheep.18 Swiss White Alpine showed higher frequency of allele V at position 136 than Swiss Oxford Down, Swiss Black-Brown Mountain and Valais Blacknose.19 Comparison of polymorphism at codon 136 in the current study with some of other breeds (20 some flock of Hampshire sheep21 with current study, but the frequency of it is higher than that of some other breeds.
Open in a separate windowIt has been found that a polymorphism at codon 171 also is associated with susceptibility to experimental scrapie in Cheviot sheep16 and natural scrapie in Suffolk sheep.22 As shown in 23 They also found that different breeds show different predominant genotypes in ewes and rams.23 Different PrP genotypes were found at codon 171 in Austrian sheep breeds, but QQ has higher frequency than others.18 In some kinds of Swiss breeds, allelic frequencies of allele Q was higher than R.19 Distribution of prion protein codon 171 genotypes in Hampshire sheep revealed that different flocks shows different patterns.21 The frequency of PrP genotypes at codon 171 in Iranian Ghezel breeds was similar to some sheep breeds, like the Suffolk breed of Oklahoma sheep, but it was completely different from others (PrP genotypes at codon 172 Breed Allelic frequency Genotypes Reference Q R H RR QR QQ QH RH HH Iranian Iranian Ghezel breeds (n = 120) 55.00 43.33 1.67 23.33 36.67 36.67 0.00 3.33 0.00 Current study Oklahoma sheep (n = 334) De Silva, et al.20 Suffolk 40.95 59.05 0.00 37.07 43.97 18.97 0.00 0.00 0.00 Hampshire 51.89 48.11 0.00 21.70 52.83 25.47 0.00 0.00 0.00 Dorset 67.75 31.25 0.00 7.95 46.59 45.45 0.00 0.00 0.00 Montadale 62.96 37.04 0.00 14.81 44.44 40.74 0.00 0.00 0.00 Hampshire (n = 201) 72.14 26.60 1.26 5.00 42.00 50.00 2.00 1.00 0.00 Youngs, et al.21 German Sheep Breeds (n = 660) Kutzer, et al.28 Bleu du Maine 37.8 62.2 0.00 46.96 30.44 22.6 0.00 0.00 0.00 Friesian Milk S. 90.45 8.9 0.65 1.27 15.3 82.8 0.00 0.00 0.64 Nolana 42.3 57.8 0.00 36.62 42.26 21.13 0.00 0.00 0.00 Suffolk 68.4 27.6 4.0 16.1 21.84 55.17 4.6 1.15 1.15 Texel 55.35 29.7 14.9 12.56 26.83 36.36 11.25 7.36 5.63 Swiss Sheep (n = 200) Gmur, et al.19 Swiss Oxford Down 32.00 68.00 - - - - - - - Swiss Black-Brown M. 70.00 30.00 - - - - - - - Valais Blacknose 85.00 15.00 - - - - - - - Swiss White Alpine 27.00 73.00 - - - - - - - Austrian Sheep (n = 112) Sipos, et al.18 Tyrolean mountain sheep 74.30 25.80 0.00 2.90 45.70 51.40 0.00 0.00 0.00 Forest sheep 77.00 19.20 3.80 11.50 15.40 69.20 0.00 0.00 3.80 Tyrolean stone sheep 81.50 14.80 3.70 0.00 29.60 62.90 7.40 0.00 0.00 Carynthian sheep 72.80 23.00 4.20 4.20 41.70 13.00 8.40 0.00 0.00
Table 1
Comparison of PrP allelic and genotype frequencies at codon 136 in different breedsBreed | A (%) | V (%) | AA (%) | AV (%) | VV (%) | Reference |
Iranian Ghezel breeds (n = 120) | 77.50 | 22.5 | 65.00 | 25.00 | 10.00 | Current study |
Oklahoma sheep (n = 334) | De Silva, et al.27 | |||||
Suffolk | 99.24 | 0.76 | 98.48 | 1.52 | 0.00 | |
Hampshire | 100 | 0.00 | 100 | 0.00 | 0.00 | |
Dorset | 92.6 | 7.94 | 87.30 | 9.52 | 3.17 | |
Montadale | 77.66 | 22.34 | 59.57 | 36.17 | 4.26 | |
Hampshire (n = 48) | 93.75 | 6.25 | 88.00 | 12.00 | 0.00 | Youngs, et al.21 |
German Sheep Breeds (n = 660) | 92.89 | 7.11 | 87.80 | 10.47 | 1.73 | Kutzer, et al.28 |
Bleu du Maine | 83.47 | 16.53 | 69.56 | 27.83 | 2.61 | |
Friesian Milk S. | 100 | 0.00 | 100 | 0.00 | 0.00 | |
Nolana | 90.13 | 9.87 | 85.90 | 8.46 | 5.64 | |
Suffolk | 100 | 0.00 | 100 | 0.00 | 0.00 | |
Texel | 90.87 | 9.13 | 82.16 | 17.41 | 0.43 | |
Swiss Sheep (n = 200) | 92.5 | 7.5 | Gmur, et al.19 | |||
Swiss Oxford Down | 93.00 | 7.00 | - | - | - | |
Swiss Black-Brown M. | 99.00 | 1.00 | - | - | - | |
Valais Blacknose | 100 | 0.00 | - | - | - | |
Swiss White Alpine | 88.00 | 22.00 | - | - | - | |
Austrian Sheep (n = 112) | 98.95 | 1.05 | 98.95 | 0.00 | 1.05 | Sipos, et al.18 |
Tyrolean mountain sheep | 100 | 0.00 | 100 | 0.00 | 0.00 | |
Forest sheep | 100 | 0.00 | 100 | 0.00 | 0.00 | |
Tyrolean stone sheep | 100 | 0.00 | 100 | 0.00 | 0.00 | |
Carynthian sheep | 95.80 | 4.20 | 95.80 | 0.00 | 4.20 |