全文获取类型
收费全文 | 315篇 |
免费 | 13篇 |
出版年
2024年 | 1篇 |
2023年 | 8篇 |
2022年 | 11篇 |
2021年 | 22篇 |
2020年 | 8篇 |
2019年 | 13篇 |
2018年 | 12篇 |
2017年 | 19篇 |
2016年 | 12篇 |
2015年 | 19篇 |
2014年 | 24篇 |
2013年 | 29篇 |
2012年 | 18篇 |
2011年 | 20篇 |
2010年 | 17篇 |
2009年 | 9篇 |
2008年 | 19篇 |
2007年 | 10篇 |
2006年 | 9篇 |
2005年 | 14篇 |
2004年 | 3篇 |
2003年 | 1篇 |
2002年 | 4篇 |
2001年 | 3篇 |
1999年 | 2篇 |
1998年 | 3篇 |
1997年 | 1篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 3篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1984年 | 1篇 |
1981年 | 1篇 |
1976年 | 1篇 |
排序方式: 共有328条查询结果,搜索用时 15 毫秒
191.
Rogy R. Ezz Eldin Marwa A. Saleh Mohammad Hayal Alotaibi Reem K. Alsuair Yahya A. Alzahrani Feras A. Alshehri Amany F. Mohamed Shaimaa M. Hafez Azza Ali Althoqapy Seham K. Khirala Mona M. Amin Yousuf A. F Azza H. AbdElwahab Mohamed S. Alesawy Ayman Abo Elmaaty Ahmed A. Al-Karmalawy 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):1098
Herein, a series of N''-benzylidene-3,4-dimethoxybenzohydrazide derivatives were designed and synthesised to target the multidrug efflux pump (MATE). The antibacterial activities were screened against S. aureus, Acinetobacter, S. typhi, E. coli, and P. aeruginosa, whereas their antifungal activities were screened against C. albicans. Compounds 4a, 4h, and 4i showed the most promising antibacterial and antifungal activities. Moreover, compounds 4h and 4i being the broader and superior members regarding their antimicrobial effects were selected to be further evaluated via in vivo testing using biochemical analysis and liver/kidney histological examination. Additionally, molecular docking was carried out to attain further deep insights into the synthesised compounds'' binding modes. Also, ADMET studies were performed to investigate the physicochemical/pharmacokinetics features and toxicity parameters of the synthesised derivatives. Finally, a structure-antimicrobial activity relationship study was established to facilitate further structural modifications in the future.
Highlights
- A series of new N''-benzylidene-3,4-dimethoxybenzohydrazide derivatives were designed and synthesised targeting the multidrug efflux pump (MATE) guided by the pharmacophoric features of the co-crystallized native inhibitor of the target protein.
- The newly synthesised compounds were assessed through in vitro, in vivo, and in silico approaches.
- Using the agar well diffusion assay, the antibacterial activities of the synthesised compounds were screened against S. aureus, Acinetobacter, S. typhi, E. coli, and P. aeruginosa, whereas, their antifungal activities were screened against C. albicans.
- The minimal inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC) of the synthesised compounds were investigated on variable microbial species.
- Compounds (4h and 4i) -as the broader and superior members regarding their antimicrobial effects- were further evaluated via in vivo testing using bio-chemical analysis and liver/kidney histological examination.
- A molecular docking study and ADMET in silico studies were performed.
- A structure-antimicrobial activity relationship study was established to facilitate further structural modifications in the future.
192.
Taseer Ahmad Taous Khan Tahira Tabassum Yahya S. Alqahtani Mater H. Mahnashi Bandar A. Alyami Ali O. Alqarni Mohammed Y. Alasmary Sultan A. Almedhesh Abdul Jabbar Shah 《Current issues in molecular biology》2022,44(7):3180
Therapeutic and/or preventive interventions using phytochemical constituents for ischemic heart disease have gained considerable attention worldwide, mainly due to their antioxidant activity. This study investigated the cardioprotective effect and possible mechanism of juglone, a major constituent of the walnut tree, using an isoproterenol (ISO)-induced myocardial infarction (MI) model in rats. Rats were pretreated for five (5) days with juglone (1, 3 mg/kg, i.p) and atenolol (1 mg/kg, i.p) in separate experiments before inducing myocardial injury by administration of ISO (80 mg/kg, s.c) at an interval of 24 h for 2 consecutive days (4th and 5th day). The cardioprotective effect of juglone was confirmed through a lead II electrocardiograph (ECG), cardiac biomarkers (cTnI, CPK, CK-MB, LDH, ALT and AST) and histopathological study. The results of our present study suggest that prior administration of juglone (1 and 3 mg/kg) proved to be effective as a cardioprotective therapeutic agent in reducing the extent of myocardial damage (induced by ISO) by fortifying the myocardial cell membrane, preventing elevated T-waves, deep Q-waves in the ECG, heart to body weight ratio, infarction and also by normalizing cardiac marker enzymes (cTnI, CPK, CK-MB, LDH, ALT and AST) and histopathological changes, such as inflammation, edema and necrosis. In conclusion, this study has identified phytochemical constituents, in particular juglone, as a potential cardioprotective agent. 相似文献
193.
Cupriavidus sp. USMAA1020 was isolated from Malaysian environment and able to synthesize poly(3-hydroxybutyrate-co-4-hydroxybutyrate), [P(3HB-co-4HB)] when grown on gamma-butyrolactone as the sole carbon source. The polyester was purified from freeze-dried cells and analyzed by nuclear magnetic resonance (NMR) spectroscopy. 1H and 13C NMR results confirmed the presence of 3HB and 4HB monomers. In a one-step cultivation process, P(3HB-co-4HB) accumulation by Cupriavidus sp. USMAA1020 was affected by carbon to nitrogen ratio (C/N). A two-step cultivation process accumulated P(3HB-co-4HB) copolyester with a higher 4HB fraction (53 mol%) in nitrogen-free mineral medium containing gamma-butyrolactone. The biosynthesis of P(3HB-co-4HB) was also achieved by using 4-hydroxybutyric acid and alkanediol as 1,4-butanediol. The composition of copolyesters varied from 32 to 51 mol% 4HB, depending on the carbon sources supplied. The copolyester produced by Cupriavidus sp. USMAA1020 has a random sequence distribution of 3-hydroxybutyrate (3HB) and 4-hydroxybutyrate (4HB) units when analyzed by nuclear magnetic resonance (NMR) spectroscopy. When gamma-butyrolactone was used as the sole carbon source, the 4HB fraction in copolyester increased from 25 to 60 mol% as the concentration of gamma-butyrolactone in the culture medium increased from 2.5 g/L to 20.0 g/L. 相似文献
194.
Valence M. K. Ndesendo Viness Pillay Yahya E. Choonara Lisa C. du Toit Eckhart Buchmann Leith C. R. Meyer Riaz A. Khan Uwe Rosin 《AAPS PharmSciTech》2010,11(2):793-808
The purpose of this study was to develop and evaluate the bioadhesivity, in vitro drug release, and permeation of an intravaginal bioadhesive polymeric device (IBPD) loaded with 3′-azido-3′-deoxythymidine
(AZT) and polystyrene sulfonate (PSS). Modified polyamide 6,10, poly(lactic-coglycolic acid), polyacrylic acid, polyvinyl
alcohol, and ethylcellulose were blended with model drugs AZT and PSS as well as radio-opaque barium sulfate (BaSO4) and then
compressed into caplet devices on a tableting press. One set of devices was coated with 2% w/v pentaerythritol polyacrylic acid (APE-PAA) while another remained uncoated. Thermal analysis was performed on the constituent
polymers as well the IBPD. The changes in micro-environmental pH within the simulated human vaginal fluid due to the presence
of the IBPD were assessed over a period of 30 days. Textural profile analysis indicated that the bioadhesivity of the APE-PAA-coated
devices (3.699 ± 0.464 N; 0.0098 ± 0.0004 J) was higher than that of the uncoated devices (1.198 ± 0.150 N; 0.0019 ± 0.0001 J).
In addition, BaSO4-facilitated X-ray imaging revealed that the IBPD adhered to pig vaginal tissue over the experimental period
of 30 days. Controlled drug release kinetics was obtained over 72 days. During a 24-h permeation study, an increase in drug
flux for both AZT (0.84 mg cm−2 h−1) and PSS (0.72 mg cm−2 h−1) was realized up to 12 h and thereafter a steady-state was achieved. The diffusion and dissolution dynamics were mechanistically
deduced based on a chemometric and molecular structure modeling approach. Overall, results suggested that the IBPD may be
sufficiently bioadhesive with desirable physicochemical and physicomechanical stability for use as a prolonged intravaginal
drug delivery device. 相似文献
195.
196.
Yahya Ali Witold Kot Zeynep Atamer J?rg Hinrichs Finn K. Vogensen Knut J. Heller Horst Neve 《Applied and environmental microbiology》2013,79(12):3628-3636
A set of 83 lytic dairy bacteriophages (phages) infecting flavor-producing mesophilic starter strains of the Leuconostoc genus was characterized, and the first in-depth taxonomic scheme was established for this phage group. Phages were obtained from different sources, i.e., from dairy samples originating from 11 German dairies (50 Leuconostoc pseudomesenteroides [Ln. pseudomesenteroides] phages, 4 Ln. mesenteroides phages) and from 3 external phage collections (17 Ln. pseudomesenteroides phages, 12 Ln. mesenteroides phages). All phages belonged to the Siphoviridae family of phages with isometric heads (diameter, 55 nm) and noncontractile tails (length, 140 nm). With the exception of one phage (i.e., phage ΦLN25), all Ln. mesenteroides phages lysed the same host strains and revealed characteristic globular baseplate appendages. Phage ΦLN25, with different Y-shaped appendages, had a unique host range. Apart from two phages (i.e., phages P792 and P793), all Ln. pseudomesenteroides phages shared the same host range and had plain baseplates without distinguishable appendages. They were further characterized by the presence or absence of a collar below the phage head or by unique tails with straight striations. Phages P792 and P793 with characteristic fluffy baseplate appendages could propagate only on other specific hosts. All Ln. mesenteroides and all Ln. pseudomesenteroides phages were members of two (host species-specific) distinct genotypes but shared a limited conserved DNA region specifying their structural genes. A PCR detection system was established and was shown to be reliable for the detection of all Leuconostoc phage types. 相似文献
197.
Shimaa A.H. Abdel Monaim Yahya E. Jad Ayman El-Faham Beatriz G. de la Torre Fernando Albericio 《Bioorganic & medicinal chemistry》2018,26(10):2788-2796
It looks that a new era of antimicrobial peptides (AMPs) started with the discovery of teixobactin, which is a “head to side-chain” cyclodepsipeptide. It was isolated from a soil gram-negative b-proteobacteria by means of a revolutionary technique. Since there, several groups have developed synthetic strategies for efficient synthesis of this peptide and its analogues as well. Herein, all chemistries reported as well as the biological activity of the analogues are analyzed. Finally, some inputs regarding new trends for the next generation of analogues are discussed. 相似文献
198.
199.
Chun-Lai T Padyukov L Dhaliwal JS Lundström E Yahya A Muhamad NA Klareskog L Alfredsson L Larsson PT Murad S;Malaysian Epidemiological Investigation of Rheumatoid Arthritis 《PloS one》2011,6(6):e21069
Background
To investigate the associations between HLA-DRB1 shared epitope (SE) alleles and rheumatoid arthritis in subsets of rheumatoid arthritis defined by autoantibodies in three Asian populations from Malaysia.Methods
1,079 rheumatoid arthritis patients and 1,470 healthy controls were included in the study. Levels of antibodies to citrullinated proteins (ACPA) and rheumatoid factors were assessed and the PCR-SSO method was used for HLA-DRB1 genotyping.Results
The proportion of ACPA positivity among Malay, Chinese and Indian rheumatoid arthritis patients were 62.9%, 65.2% and 68.6%, respectively. An increased frequency of SE alleles was observed in ACPA-positive rheumatoid arthritis among the three Asian ethnic groups. HLA-DRB1*10 was highly associated with rheumatoid arthritis susceptibility in these Asian populations. HLA-DRB1*0405 was significantly associated with susceptibility to rheumatoid arthritis in Malays and Chinese, but not in Indians. HLA-DRB1*01 did not show any independent effect as a risk factor for rheumatoid arthritis in this study and HLA-DRB1*1202 was protective in Malays and Chinese. There was no association between SE alleles and ACPA- negative rheumatoid arthritis in any of the three Asian ethnic groups.Conclusion
The HLA-DRB1 SE alleles increase the risk of ACPA-positive rheumatoid arthritis in all three Asian populations from Malaysia. 相似文献200.
The purpose of this study was to formulate drug-loaded polyelectrolyte matrices constituting blends of pectin, chitosan (CHT)
and hydrolyzed polyacrylamide (HPAAm) for controlling the premature solvation of the polymers and modulating drug release.
The model drug employed was the highly water-soluble antihistamine, diphenhydramine HCl (DPH). Polyelectrolyte complex formation
was validated by infrared spectroscopy. Matrices were characterized by textural profiling, porositometry and SEM. Drug release
studies were performed under simulated gastrointestinal conditions using USP apparatus 3. FTIR spectra revealed distinctive
peaks indicating the presence of –COO− symmetrical stretching (1,425–1,390 cm−1) and -NH3+ deformation (1,535 cm−1) with evidence of electrostatic interaction between the cationic CHT and anionic HPAAm corroborated by molecular mechanics
simulations of the complexes. Pectin–HPAAm matrices showed electrostatic attraction due to residual –NH2 and –COO− groups of HPAAm and pectin, respectively. Textural profiling demonstrated that CHT-HPAAm matrices were most resilient at
6.1% and pectin–CHT–HPAAm matrices were the least (3.9%). Matrix hardness and deformation energy followed similar behavior.
Pectin–CHT–HPAAm and CHT–HPAAm matrices produced type IV isotherms with H3 hysteresis and mesopores (22.46 nm) while pectin–HPAAm
matrices were atypical with hysteresis at a low P/P0 and pore sizes of 5.15 nm and a large surface area. At t
2 h, no DPH was released from CHT–HPAAm matrices, whereas 28.2% and 82.2% was released from pectin–HPAAm and pectin–CHT–HPAAm
matrices, respectively. At t
4 h, complete DPH release was achieved from pectin–CHT–HPAAm matrices in contrast to only 35% from CHT–HPAAm matrices. This revealed
the release-modulating capability of each matrix signifying their applicability in controlled oral drug delivery applications. 相似文献