全文获取类型
收费全文 | 645篇 |
免费 | 29篇 |
国内免费 | 1篇 |
出版年
2024年 | 2篇 |
2023年 | 14篇 |
2022年 | 15篇 |
2021年 | 38篇 |
2020年 | 22篇 |
2019年 | 32篇 |
2018年 | 30篇 |
2017年 | 22篇 |
2016年 | 35篇 |
2015年 | 50篇 |
2014年 | 38篇 |
2013年 | 80篇 |
2012年 | 46篇 |
2011年 | 44篇 |
2010年 | 25篇 |
2009年 | 19篇 |
2008年 | 23篇 |
2007年 | 21篇 |
2006年 | 19篇 |
2005年 | 21篇 |
2004年 | 17篇 |
2003年 | 13篇 |
2002年 | 14篇 |
2001年 | 2篇 |
1999年 | 2篇 |
1998年 | 1篇 |
1996年 | 2篇 |
1994年 | 2篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 5篇 |
1986年 | 3篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1975年 | 3篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有675条查询结果,搜索用时 15 毫秒
41.
Mansoureh Soleimani Fereshteh Golab Akram Alizadeh Sara Rigi Zeinab Nazarian Samani Gelareh Vahabzadeh Tahmineh Peirovi Maryam Sarbishegi Majid Katebi Fereshteh Azedi 《Journal of cellular physiology》2019,234(10):18720-18730
Electromagnetic fields (EMFs) are reported to interfere with chemical reactions involving free radical production. Coenzyme Q10 (CoQ10) is a strong antioxidant with some neuroprotective activities. The purpose of this study was to examine and compare the neuroprotective effects of EMF and CoQ10 in a mouse model of hippocampal injury. Hippocampal injury was induced in mature female mice (25–30 g), using an intraperitoneal injection of trimethyltin hydroxide (TMT; 2.5 mg/kg). The experimental groups were exposed to EMF at a frequency of 50 Hz and intensity of 5.9 mT for 7 hr daily over 1 week or treated with CoQ10 (10 mg/kg) for 2 weeks following TMT injection. A Morris water maze apparatus was used to assess learning and spatial memory. Nissl staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) tests were also performed for the histopathological analysis of the hippocampus. Antiapoptotic genes were studied, using the Western blot technique. The water maze test showed memory improvement following treatment with CoQ10 and coadministration of CoQ10 + EMF. The Nissl staining and TUNEL tests indicated a decline in necrotic and apoptotic cell count following treatment with CoQ10 and coadministration of CoQ10 + EMF. The Western blot study indicated the upregulation of antiapoptotic genes in treatment with CoQ10, as well as coadministration. Also, treatment with EMF had no significant effects on reducing damage induced by TMT in the hippocampus. According to the results, EMF had no significant neuroprotective effects in comparison with CoQ10 on hippocampal injury in mice. Nevertheless, coadministration of EMF and CoQ10 could improve the neuroprotective effects of CoQ10. 相似文献
42.
Saeed Farzamfar Akram Hasanpour Niloufar Nazeri Hengameh Razavi Majid Salehi Shilan Shafei Vajiheh T. Nooshabadi Ahmad Vaez Arian Ehterami Hamed Sahrapeyma Jafar Ai 《Journal of cellular physiology》2019,234(8):12290-12300
Acute renal failure (ARF) is a clinical challenge that is highly resistant to treatment, and its high rate of mortality is alarming. Ischemia–reperfusion injury (IRI) is the most common cause of ARF. Especially IRI is implicated in kidney transplantation and can determine graft survival. Although the exact pathophysiology of renal IRI is unknown, the role of inflammatory responses has been elucidated. Because mesenchymal stromal cells (MSCs) have strong immunomodulatory properties, they are under extensive investigation as a therapeutic modality for renal IRI. Extracellular vesicles (EVs) play an integral role in cell-to-cell communication. Because the regenerative potential of the MSCs can be recapitulated by their EVs, the therapeutic appeal of MSC-derived EVs has dramatically increased in the past decade. Higher safety profile and ease of preservation without losing function are other advantages of EVs compared with their producing cells. In the current review, the preliminary results and potential of MSC-derived EVs to alleviate kidney IRI are summarized. We might be heading toward a cell-free approach to treat renal IRI. 相似文献
43.
Variation of toxigenic Vibrio cholerae O1 in the aquatic environment of Bangladesh and its correlation with the clinical strains 总被引:3,自引:0,他引:3
Islam MS Talukder KA Khan NH Mahmud ZH Rahman MZ Nair GB Siddique AK Yunus M Sack DA Sack RB Huq A Colwell RR 《Microbiology and immunology》2004,48(10):773-777
The diversity of toxigenic V. cholerae O1 in the aquatic environment of Bangladesh is not known. A total of 18 environmental and 18 clinical strains of toxigenic V. cholerae O1 were isolated simultaneously from four different geographical areas and tested for variation by the pulsed-field gel electrophoresis method. Environmental strains showed diversified profiles and one of the profiles was common to some environmental strains and most clinical strains. It appears that one clone has an advantage over others to cause disease. These findings suggest that the study of the molecular ecology of V. cholerae O1 in relation to its environmental reservoir is important in identifying virulent strains that cause disease. 相似文献
44.
Chohan ZH Pervez H Khan KM Rauf A Supuran CT 《Journal of enzyme inhibition and medicinal chemistry》2004,19(1):51-56
A method is described for the preparation of novel cephalexin-derived furanyl-, thiophenyl-, pyrrolyl-, salicylyl- and pyridyl-containing compounds showing potent antibacterial activity. The binding of these newly synthesized antibacterial agents with metal ions such as cobalt(II), copper(II), nickel(II) and zinc(II) has been studied and their inhibitory properties against various bacterial species such as Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae are also reported. These results suggest that metal ions to possess an important role in the designing of metal-based antibacterials and that such complexes are more effective against infectious diseases compared to the uncomplexed drugs. 相似文献
45.
Chohan ZH Scozzafava A Supuran CT 《Journal of enzyme inhibition and medicinal chemistry》2002,17(4):261-266
Condensation reactions of 1,1'-diacetylferrocene with different heteroaromatic amines such as, 2-amino-1,3,4-thiadiazole, 5-aminotetrazole and 3-amino-1,2,4-triazole to form unsymmetrically 1,1'-disubstituted ferrocenes have been studied. The obtained compounds have been further investigated for their liganding and biological properties upon chelation with Co(II), Cu(II), Ni(II) and Zn(II) metal ions. The synthesized compounds have been characterized by physical, spectral and analytical data and have been screened against pathogenic bacterial strains e.g., Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus, showing moderate activity as antibacterials in vitro. 相似文献
46.
Chohan ZH Iqbal MS Iqbal HS Scozzafava A Supuran CT 《Journal of enzyme inhibition and medicinal chemistry》2002,17(2):87-91
Mononuclear and binuclear transition metal [Co(II), Cu(II), Ni(II) and Zn(II)] acetylsalicylates of the type [M(L)2], [M(L)2Cl2] and [(M)2(L)4] have been prepared and characterized on the basis of their physical, spectral and analytical data. The complexes have been investigated in an in vivo animal model for anti-inflammatory activity and show a better effect and a more potent action than acetylsalicylic acid. 相似文献
47.
S-Adenosylmethionine decarboxylase (AdoMetDC) is a key enzyme of the polyamine synthetic pathway providing decarboxylated S-adenosylmethionine for the formation of spermidine and spermine, respectively. The catalytic activity of the AdoMetDC from the free-living nematode Caenorhabditis elegans highly depends on the presence of an activator molecule. Putrescine, a well-known stimulator of mammalian AdoMetDC activity, enhances the catalytic activity of the nematode enzyme 350-fold. Putrescine stimulation is discussed as a regulatory mechanism to relate putrescine abundance with the synthesis of spermidine and spermine. In contrast to any other known AdoMetDC, spermidine and spermine also represent significant activators of the nematode enzyme. However, the biological significance of the observed stimulation by these higher polyamines is unclear. Although C. elegans AdoMetDC exhibits a low specificity toward activator molecules, the amino acid residues that were shown to be involved in putrescine binding of the human enzyme are conserved in the nematode enzyme. Exchanging these residues by site-directed mutagenesis indicates that at least three residues, Thr192, Glu194 and Glu274, most likely contribute to activator binding in the C. elegans AdoMetDC. Interestingly, the mutant Glu194Gln exhibits a 100-fold enhanced basal activity in the absence of any stimulator, suggesting that this mutant protein mimics the conformational change usually induced by activator molecules. Furthermore, site-directed mutagenesis revealed that at least Glu33, Ser83, Arg91 and Lys95 are involved in posttranslational processing of C. elegans AdoMetDC. 相似文献
48.
The Physiological,Biochemical and Molecular Roles of Brassinosteroids and Salicylic Acid in Plant Processes and Salt Tolerance 总被引:2,自引:0,他引:2
Plant hormones regulate plant growth and development by affecting an array of cellular, physiological, and developmental processes, including, but not limited to, cell division and elongation, stomatal regulation, photosynthesis, transpiration, ion uptake and transport, initiation of leaf, flower and fruit development, and senescence. Environmental factors such as salinity, drought, and extreme temperatures may cause a reduction in plant growth and productivity by altering the endogenous levels of plant hormones, sensitivity to plant hormones, and/or signaling pathways. Molecular and physiological studies have determined that plant hormones and abiotic stresses have interactive effects on a number of basic biochemical and physiological processes, leading to reduced plant growth and development. Various strategies have been considered or employed to maximize plant growth and productivity under environmental stresses such as salt-stress. A fundamental approach is to develop salt-tolerant plants through genetic means. Breeding for salt tolerance, however, is a long-term endeavor with its own complexities and inherent difficulties. The success of this approach depends, among others, on the availability of genetic sources of tolerance and reliable screening techniques, identification and successful transfer of genetic components of tolerance to desired genetic backgrounds, and development of elite breeding lines and cultivars with salt tolerance and other desirable agricultural characteristics. Such extensive processes have delayed development of successful salt-tolerant cultivars in most crop species. An alternative and technically simpler approach is to induce salt tolerance through exogenous application of certain plant growth–regulating compounds. This approach has gained significant interest during the past decade, when a wealth of new knowledge has become available on the beneficial roles of the six classes of plant hormones (auxins, gibberellins, cytokinins, abscisic acid, ethylene, and brassinosteroids) as well as several other plant growth–regulating substances (jasmonates, salicylates, polyamines, triacontanol, ascorbic acid, and tocopherols) on plant stress tolerance. Among these, brassinosteroids (BRs) and salicylic acid (SA) have been studied most extensively. Both BRs and SA are ubiquitous in the plant kingdom, affecting plant growth and development in many different ways, and are known to improve plant stress tolerance. In this article, we review and discuss the current knowledge and possible applications of BRs and SA that could be used to mitigate the harmful effects of salt-stress in plants. We also discuss the roles of exogenous applications of BRs and SA in the regulation of various biochemical and physiological processes leading to improved salt tolerance in plants. 相似文献
49.
Stéphanie Blanchard Anthony D. William Angeline C.-H. Lee Anders Poulsen Ee Ling Teo Weiping Deng Noah Tu Evelyn Tan Kay Lin Goh Wai Chung Ong Chee Pang Ng Kee Chuan Goh Zahid Bonday Eric T. Sun 《Bioorganic & medicinal chemistry letters》2010,20(8):2443-2447
A series of alkenyl indazoles were synthesized and evaluated in Aurora kinase enzyme assays. Several promising leads were optimized for selectivity towards Aurora B. Excellent binding affinity and good selectivity were achieved with optimized compounds in isolated Aurora subfamily assays. 相似文献
50.
Iain D. Hay Zahid U. Rehman Bernd H. A. Rehm 《Applied and environmental microbiology》2010,76(6):1806-1812
The ubiquitous opportunistic human pathogen Pseudomonas aeruginosa secretes a viscous extracellular polysaccharide, called alginate, as a virulence factor during chronic infection of patients with cystic fibrosis. In the present study, it was demonstrated that the outer membrane protein AlgE is required for the production of alginate in P. aeruginosa. An isogenic marker-free algE deletion mutant was constructed. This strain was incapable of producing alginate but did secrete alginate degradation products, indicating that polymerization occurs but that the alginate chain is subsequently degraded during transit through the periplasm. Alginate production was restored by introducing the algE gene. The membrane topology of the outer membrane protein AlgE was assessed by site-specific insertions of FLAG epitopes into predicted extracellular loop regions.Pseudomonas aeruginosa is an ubiquitous opportunistic human pathogen responsible for chronic infections of the lungs of patients with cystic fibrosis (CF), in whom it is the leading cause of mortality and morbidity (9). The establishment of a chronic infection in the lungs of patients with CF coincides with the switch of P. aeruginosa to a stable mucoid variant, producing copious amounts of the exopolysaccharide alginate; this is typically a poor prognostic indicator for these patients (24, 31). Alginate is a linear unbranched exopolysaccharide consisting of 1,4-linked monomers of β-d-mannuronic acid and its C-5 epimer, α-l-guluronic acid, which is known to be produced by only two bacterial genera, Pseudomonas and Azotobacter (34). The switch to a mucoid phenotype coincides with the appearance of a 54-kDa protein in the outer membrane; this protein has been identified and has been designated AlgE (13, 31).The genes encoding the alginate biosynthesis machinery are located within a 12-gene operon (algD-alg8-alg44-algK-algE-algG-algX-algL-algI-algJ-algF-algA). AlgA and AlgD, along with AlgC (not encoded in the operon), are involved in precursor synthesis (34). Alg8 is the catalytic subunit of the alginate polymerase located at the inner membrane (35). AlgG is a C-5 mannuronan epimerase (19). AlgK contains four putative Sel1-like repeats, similar to the tetratricopeptide repeat motif often found in adaptor proteins involved in the assembly of multiprotein complexes (3, 10). AlgX shows little homology to any known protein, and its role is unclear (14). Knockout mutants of AlgK, AlgG, and AlgX have nonmucoid phenotypes, although they produce short alginate fragments, due to the activity of the alginate lyase (AlgL), which degrades the nascent alginate (1, 14, 19-21, 36). AlgF, AlgI, and AlgJ are involved in acetylation of alginate, but they are not ultimately required for its production (12). The membrane-anchored protein, Alg44, is required for polymerization and has a PilZ domain for the binding of c-di-GMP, a secondary messenger essential for alginate production (16, 25, 33). The periplasmic C terminus of Alg44 shares homology with the membrane fusion proteins involved in the bridging of the periplasm in multidrug efflux pumps (11, 43). The periplasmic alginate lyase, AlgL, appears to be required for the translocation of intact alginate across the periplasm (1, 26). AlgE is an outer membrane, anion-selective channel protein through which alginate is presumably secreted (30). A protein complex or scaffold through which the alginate chain can pass and be modified and which spans the periplasm bridging the polymerase located (Alg8) at the outer membrane pore (AlgE) has been proposed (21). Indeed, it has been demonstrated that both the inner and the outer membranes are required for the in vitro polymerization of alginate (35).The requirement of AlgE for the biosynthesis of alginate in P. aeruginosa was first observed by complementation of an alginate-negative mutant derived by chemical mutagenesis with a DNA fragment containing algE (8) Secondary structure predictions suggested that AlgE forms an 18-stranded β barrel with extended extracellular loops. Several of these loops show high densities of charged amino acids, suggesting a functional role in the translocation of the anionic alginate polymer (29, 30). Preliminary analysis of AlgE crystals has been reported (48).In this study, the role of AlgE in alginate biosynthesis was investigated and the membrane topology of AlgE was assessed by site-directed insertion mutagenesis. 相似文献