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41.
Nawaf A. Alsaif Mohammed S. Taghour Mohammed M. Alanazi Ahmad J. Obaidullah Abdulrahman A. Al-Mehizia Manal M. Alanazi Saleh Aldawas Alaa Elwan Hazem Elkady 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):1093
Herein, a new wave of bis([1, 2, 4]triazolo)[4,3-a:3'',4''-c]quinoxaline derivatives have been successfully designed and synthesised. The synthesised derivatives were biologically investigated for their cytotoxic activities against HepG2 and MCF-7. Also, the tested compounds were further examined in vitro for their VEGFR-2 inhibitory activity. The most promising derivative 23j was further investigated for its apoptotic behaviour in HepG2 cell lines using flow cytometric and western-plot analyses. Additional in-silico studies were performed to predict how the synthesised compounds can bind to VEGFR-2 and to determine the drug-likeness profiling of these derivatives. The results revealed that compounds 23a, 23i, 23j, 23l, and 23n displayed the highest antiproliferative activities against the two cell lines with IC50 values ranging from 6.4 to 19.4 µM. Furthermore, compounds 23a, 23d, 23h, 23i, 23j, 23l, 23 m, and 23n showed the highest VEGFR-2 inhibitory activities with IC50 values ranging from 3.7 to 11.8 nM, comparing to sorafenib (IC50 = 3.12 nM). Moreover, compound 23j arrested the HepG2 cell growth at the G2/M phase and induced apoptosis by 40.12% compared to the control cells (7.07%). As well, such compound showed a significant increase in the level of caspase-3 (1.36-fold), caspase-9 (2.80-fold), and BAX (1.65-fold), and exhibited a significant decrease in Bcl-2 level (2.63-fold). 相似文献
42.
Sadaf Mutahir Muhammad Asim Khan Abdulrahman Abdulaziz Almehizia Amr Salah Abouzied Nasrin Eldirdiri Khalifa Ahmed Mohamed Naglah Haishan Deng Moamen Salaheldeen Refat Weam Mohamed Ali Khojali Bader Huwaimel 《化学与生物多样性》2023,20(8):e202300241
Mannich bases consisting of 1,3,4-oxadiazole-2-thione ( 3 a – 3 l ) bearing various substituents were synthesized and found potent jack bean urease inhibitors. The prepared compounds showed significantly good inhibitory activities with IC50 values from 9.45±0.05 to 267.42±0.23 μM. The compound 3 k containing 4-chlorophenyl (−R) and 4-hydroxyphenyl (−R′) was most active with IC50 9.45±0.05 μM followed by 3 e (IC50 22.52±0.15 μM) in which −R was phenyl and −R′ was isopropyl group. However, when both −R and −R′ were either 4-chlorophenyl groups ( 3 l ) or only −R′ was 4-nitrophenyl ( 3 i ), both compounds were found inactive. The detailed binding affinities of the produced compounds with protein were explored through molecular docking and data-supported in-vitro enzyme inhibition profiles. Drug likeness was confirmed by in silico ADME investigations and molecular orbital analysis (HOMO-LUMO) and electrostatic potential maps were got from DFT calculations. ESP maps exposed that there are two potential binding sites with the most positive and most negative parts. 相似文献
43.
Shilu Mathew Muhammad Faheem Abdulrahman L Al-Malki Taha A Kumosani Ishtiaq Qadri 《Bioinformation》2015,11(4):189-195
Epilepsy is a neurological disorder affecting more than 50 million people worldwide. It can be controlled by antiepileptic drugs
(AEDs) but more than 30% patients are still resistant to AEDs. To overcome this problem, researchers are trying to develop novel
approaches to treat epilepsy including the use of herbal medicines. The γ-amino butyric acid type-A receptor associated protein
(GABARAP) is ubiquitin-like modifier implicated in the intracellular trafficking of GABAAR. An in silico mutation was created at
116 amino acid position G116A, and an in silico study was carried out to identify the potential binding inhibitors (with antiepileptic
properties) against the active sites of GABARAP. Five different plant derived compounds namely (a) Aconitine (b) Berberine (c)
Montanine (d) Raubasine (e) Safranal were selected, and their quantitative structure-activity relationships (QSAR) have been
conducted to search the inhibitory activity of the selected compounds. The results have shown maximum number of hydrogen
bond (H-bond) interactions of Raubasine with highest interaction energy among all of the five compounds. So, Raubasine could be
the best fit ligand of GABARAP but in vitro, and in vivo studies are necessary for further confirmation. 相似文献
44.
45.
Badr Hadhidh Alharbi Mohammad Jahangir Pasha Abdulrahman Hussein Alhudhodi Abdulilah Khalid Alduwais 《Soil & Sediment Contamination》2018,27(8):674-691
ABSTRACTSpills and leakage from underground fuel storage tanks (UFSTs) can potentially contaminate soil and groundwater and pose harmful effects to public health and the environment. This study evaluated the feasibility of using volatile organic compounds (VOCs), total petroleum hydrocarbons (TPHs), electrical conductivity (EC), and pH to examine the contamination caused by leaking UFSTs. Screening water assessments for VOCs and general water quality parameters were conducted on the premises of 53 gas stations in Riyadh, Saudi Arabia, to identify potentially contaminated sites, and 25 ground bores were drilled for the quantification of TPH concentrations, EC, and pH values in 407 soil samples. The experimental approach followed in this study included geochemical analyses based on borehole drilling at five targeted gas stations, analyses of water samples from underground storage reservoirs, and analyses of soil core samples obtained from different depths to determine the degree of TPH contamination. Thirty-five VOCs were identified in the water samples collected from gas stations. Methylene chloride, tribromomethane, toluene, chlorobenzene, dibromochloromethane, and benzene were frequently encountered in most of the water samples. Some of these samples exceeded the World Health Organization and Saudi Arabian guidelines for acceptable levels of pH, total dissolved solids, chloride, nitrate, sulfate, calcium, and total hardness. The measured TPH levels were clearly indicative of subsoil contamination and subsequent accumulation in soil over time, particularly at depths of 1–6 m; there was not a noticeable dependence or impact on pH. 相似文献
46.
Bright Varghese Mushira Enani Abdulrahman Alrajhi Sameera Al Johani Ali Albarak Sahar Althawadi Noura Elkhizzi Hawra AlGhafli Mohammed Shoukri Sahal Al - Hajoj 《Respiratory research》2018,19(1):259
Background
Growing evidences suggested that the Mycobacterium tuberculosis complex (MTBC) lineages can determine the clinical outcome of pulmonary and extra-pulmonary tuberculosis. However, limited data only available revealing such association of bacterial genotypes and clinical phenotypes from immigrant rich countries.Methods
A multicenter study has been carried out on a collection of 2092 (1003 extrapulmonary and 1089 pulmonary) MTBC isolates. Genotyping of all the isolates were carried out by spoligotyping and 24 loci based MIRU-VNTR typing.Results
Demographically domination of young Saudi nationals (61.4%) and men (61.2%) were found in this cohort. Lymph nodes (62.4%) and gastrointestinal sites (16.7%) were the most common anatomical sites of infection. The predominant lineages were Delhi/CAS (26.9%), EAI (14.2%) and Ghana (9.9%). Mycobacterium africanum type I and II were reported for the first time in the country among extrapulmonary cases. ‘Ancestral’ lineages M.bovis (OR-5.22; 95% CI-2.23-8.22, p-?<?0.001) and Delhi/CAS (OR-0.57; 95% CI-0.411-0.734, p-?<?0.001) were directly associated with lymph node tuberculosis and gastrointestinal tuberculosis (M. bovis-OR-0.33; 95% CI-0.085-0.567, p-0.001 and Delhi/CAS-OR-1.87; 95% CI-1.22-2.53, p-?<?0.001) respectively. Among the ‘Modern’ lineages, EAI showed significant association to central nervous system tuberculosis (OR-1.98; 95% CI-0.76-3.19, p-0.04) and Uganda-I to gastrointestinal tuberculosis (OR-2.41; 95% CI-0.77-4.06, p-0.02).Conclusions
The findings substantially contribute to the emerging evidences that MTBC lineages influence disease phenotypes and epidemiological consequences.47.
Gingerenone A Attenuates Monocyte‐Endothelial Adhesion via Suppression of I Kappa B Kinase Phosphorylation 下载免费PDF全文
Hee Joo Kim Joe Eun Son Jae Hwan Kim Charles C. Lee Hee Yang Soonham Sami Yaghmoor Youssri Ahmed Jehad Mustafa Yousef Khalid Omer Abualnaja Abdulrahman Labeed Al‐Malki Taha Abdullah Kumosani Jong Hun Kim Jung Han Yoon Park Chang Yong Lee Jong‐Eun Kim Ki Won Lee 《Journal of cellular biochemistry》2018,119(1):260-268
48.
Abdulrahman Nabeel Jaballah Maiy Poomakkoth Noufira Riaz Sadaf Abdelaziz Somaia Issa Aya Mraiche Fatima 《Molecular and cellular biochemistry》2016,420(1-2):21-28
49.
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
50.
Piperlongumine is a natural alkaloid extracted from piper plants which has been used traditionally for the treatment of certain diseases. This compound shows interesting in vitro pharmacological activity such as selective anticancer activity and higher cytotoxicity than methotrexate, cyclophosphamide and adriamycin on breast, colon, and osteosarcoma cancers, respectively. However, the physicochemical properties for this compound have not been well characterized. In this research, preformulation studies for piperlongumine have been performed to determine factors which influence solubility and stability which, in turn, can be used to assist future formulation development. The solubility of piperlongumine in water was found to be approximately 26 μg/ml. Using 10% polysorbate 80 as a surfactant resulted in a 27 fold increase in solubility. Cosolvents and cyclodextrins afforded concentrations of 1 mg/ml and higher. The pH degradation rate profile for piperlongumine at various temperatures shows significant instability of the drug at pH values ≥ 7 and 3, and maximum stability around pH 4. It was estimated that it would take approximately 17 weeks for piperlongumine to degrade by 10% at 25°C, pH 4. Additionally, piperlongumine showed marked photo-degradation upon exposure to an ultraviolet light source, especially in aqueous media. 相似文献