全文获取类型
收费全文 | 411篇 |
免费 | 15篇 |
国内免费 | 2篇 |
出版年
2023年 | 7篇 |
2022年 | 22篇 |
2021年 | 17篇 |
2020年 | 11篇 |
2019年 | 8篇 |
2018年 | 10篇 |
2017年 | 9篇 |
2016年 | 15篇 |
2015年 | 26篇 |
2014年 | 22篇 |
2013年 | 30篇 |
2012年 | 30篇 |
2011年 | 26篇 |
2010年 | 21篇 |
2009年 | 17篇 |
2008年 | 25篇 |
2007年 | 24篇 |
2006年 | 23篇 |
2005年 | 17篇 |
2004年 | 13篇 |
2003年 | 9篇 |
2002年 | 11篇 |
2001年 | 3篇 |
2000年 | 1篇 |
1998年 | 2篇 |
1996年 | 5篇 |
1994年 | 2篇 |
1992年 | 1篇 |
1990年 | 1篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1984年 | 6篇 |
1983年 | 1篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1971年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有428条查询结果,搜索用时 15 毫秒
401.
Konstantinos Paraskevopoulos Michael A. Hough R. Gary Sawers Robert R. Eady S. Samar Hasnain 《Journal of biological inorganic chemistry》2007,12(6):789-796
Cu-containing nitrite reductases (NiRs) perform the reduction of nitrite to NO via an ordered mechanism in which the delivery of a proton and an electron to the catalytic type 2 Cu site is highly orchestrated. Electron transfer from a redox partner protein, azurin or pseudoazurin, to the type 1 Cu site is assumed to occur through the formation of a protein-protein complex. We report here a new crystal form in space group P2(1)2(1)2(1) of the Met144Leu mutant of NiR from Alcaligenes xylosoxidans (AxNiR), revealing a head-to-head packing motif involving residues around the hydrophobic patch of domain 1. Superposition of the structure of azurin II with that of domain 1 of one of the Met144Leu molecules provides the first glimpse of an azurin II-NiR protein-protein complex. Mutations of two of the residues of AxNiR, Trp138His (Barrett et al. in Biochemistry 43:16311-16319, 2004) and Met87Leu, highlighted in the AxNiR-azurin complex, results in substantially decreased activity when azurin is used as the electron donor instead of methyl viologen, providing direct evidence for the importance of this region for complex formation. 相似文献
402.
Dalia Mohamed Ali Mohamed H. Mahmoud Rehab Ahmed Rifaai Michael Atef Fawzy Medhat Atta Nermeen N. Welson Gaber El-Saber Batiha Athanasios Alexiou Marios Papadakis Walaa Yehia Abdelzaher 《Journal of cellular and molecular medicine》2023,27(12):1735-1744
The present study aimed to identify the possible protective effect of diacerein (DIA) on gentamicin (GNT)-induced parotid toxicity in rats. DIA was administered in the presence and absence of GNT. Thirty-two Wistar adult male rats were randomly arranged into four groups: control, DIA (50 mg/kg/day), GNT (100 mg/kg) and GNT+DIA groups for 8 days. Parotid oxidative stress parameters, besides inflammatory and apoptotic biomarkers, were evaluated. Salivary flow rate, transient receptor potential canonical 1 (TRCP1), and C/EBP homologous protein (CHOP) in parotid tissue were measured. A parotid histopathological examination and an interleukin-1 beta (IL-1β) immunohistochemical study were also performed. GNT significantly increased parotid oxidative stress, inflammatory, apoptotic and CHOP biomarkers with decreased salivary flow rate and TRCP1 level. A histopathological picture of parotid damage and high IL-1β immunoexpression were detected. DIA significantly normalized the distributed oxidative, inflammatory and apoptotic indicators, CHOP and TRCP1, with a prompt improvement in the histopathological picture and a decrease in IL-1β immunoexpression. These results reported that DIA protects against GNT-induced parotid toxicity via modulation of TLR4/NF-κB/IL-1β and TRPC1/CHOP signalling pathways. 相似文献
403.
Samar M. Al-Tantawy Salma M. Eraky Laila A. Eissa 《Journal of biochemical and molecular toxicology》2023,37(10):e23430
Diabetic nephropathy (DN) is a worldwide issue that eventually leads to end-stage renal failure, with limited therapeutic options. Prior research has revealed that gold nanoparticles (AuNPs) have a substantial antidiabetic impact. In addition, sodium-glucose cotransporter2 (SGLT2) inhibitors, including dapagliflozin (DAPA), had renoprotective impact on DN. Therefore, this research attempted to determine the potential AuNPs and DAPA impacts in ameliorating experimentally DN induction and the underlying mechanisms focusing on miR-192 and miR-21, correlating them with autophagy, apoptosis, fibrosis, and oxidative stress. Diabetes induction was through a single intraperitoneal streptozotocin (55 mg/kg) injection, and rats with diabetes received AuNPs (2.5 mg/kg/day) as well as DAPA (2 mg/kg/day) for 7 weeks as a treatment. AuNPs and DAPA treatment for 7 weeks substantially alleviated DN. AuNPs and DAPA significantly increased catalase (CAT) activity as well as serum total antioxidant capacity (TAC), along with a substantial decline in malondialdehyde (MDA). AuNPs and DAPA treatment alleviated renal fibrosis as they decreased transforming growth factorß1(TGF-ß1) as well as matrix metalloproteinase-2 (MMP-2) renal expression, decreased apoptosis through alleviating the proapoptotic gene (caspase-3) renal expression and increased the antiapoptotic gene (Bcl-2) renal expression, and increased autophagy as they increased LC-3 as well as Beclin-1 renal expression. Autophagy activation, inhibition of apoptosis, and renal fibrosis could be due to their inhibitory impact on miR-192 and miR-21 renal expression. AuNPs and DAPA have a protective effect on DN in rats by targeting miR-192 and miR-21 and their downstream pathways, including fibrosis, apoptosis, autophagy, and oxidative stress. 相似文献
404.
George Abu‐Aqil Leah Tsror Elad Shufan Samar Adawi Shaul Mordechai Mahmoud Huleihel Ahmad Salman 《Journal of biophotonics》2020,13(5)
Pectobacterium and Dickeya spp. are soft rot Pectobacteriaceae that cause aggressive diseases on agricultural crops leading to substantial economic losses. The accurate, rapid and low‐cost detection of these pathogenic bacteria are very important for controlling their spread, reducing the consequent financial loss and for producing uninfected potato seed tubers for future generations. Currently used methods for the identification of these bacterial pathogens at the strain level are based mainly on molecular techniques, which are expensive. We used an alternative method, infrared spectroscopy, to measure 24 strains of five species of Pectobacterium and Dickeya. Measurements were then analyzed using machine learning methods to differentiate among them at the genus, species and strain levels. Our results show that it is possible to differentiate among different bacterial pathogens with a success rate of ~99% at the genus and species levels and with a success rate of over 94% at the strain level. 相似文献
405.
406.
407.
Zhengrui Xi Lorne Zinman Danielle Moreno Jennifer Schymick Yan Liang Christine Sato Yonglan Zheng Mahdi Ghani Samar Dib Julia Keith Janice Robertson Ekaterina Rogaeva 《American journal of human genetics》2013,92(6):981-989
The G4C2 repeat expansion in C9orf72 is the most common known cause of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). We tested the hypothesis that the repeat expansion causes aberrant CpG methylation near the G4C2 repeat, which could be responsible for the downregulation of gene expression. We investigated the CpG methylation profile by two methods using genomic DNA from the blood of individuals with ALS (37 expansion carriers and 64 noncarriers), normal controls (n = 76), and family members of 7 ALS probands with the expansion. We report that hypermethylation of the CpG island 5′ of the G4C2 repeat is associated with the presence of the expansion (p < 0.0001). A higher degree of methylation was significantly correlated with a shorter disease duration (p < 0.01), associated with familial ALS (p = 0.009) and segregated with the expansion in 7 investigated families. Notably, we did not detect methylation for either normal or intermediate alleles (up to 43 repeats), bringing to question the current cutoff of 30 repeats for pathological alleles. Our study raises several important questions for the future investigation of large data sets, such as whether the degree of methylation corresponds to clinical presentation (ALS versus FTLD). 相似文献
408.
Hala U Gali-Muhtasib Makhluf J Haddadin Musa Z Nazer Nicole M Sodir Samar W Maalouf 《Cancer immunology, immunotherapy : CII》1998,15(4):262-269
2-benzoyl-3-phenylquinoxaline 1,4-dioxide (BPQ) and other substituted quinoxaline 1,4-dioxides (QdO) were tested for their
ability to inhibit the stimulations of ornithine decarboxylase (ODC) enzyme activity and DNA synthesis, two biochemical markers
linked to skin tumour promotion by ultraviolet B (UVB) radiation. Topical application of BPQ on the dorsal skin of hairless
mice was found to inhibit in a dose-dependent manner UVB-induced ODC activity and DNA synthesis. When applied 20 min before
UVB radiation, a dose of 17 mg BPQ applied in 0.4 ml of vehicle inhibited UVB-induced ODC activity and DNA synthesis by 95%
and 85%, respectively. This inhibitory effect is dependent on the time of administration of BPQ relative to UVB radiation,
with a generally greater inhibition observed when this compound is applied before rather than after UVB treatment. The inhibitory
abilities of the other QdO on the ODC and DNA responses induced by UVB radiation greatly varied and appear to be dependent
on the structure of the compounds and their metabolic activation in the skin following irradiation. The remarkable effectiveness
of BPQ against the ODC and DNA markers of UVB promotion is also observed following multiple applications of this agent. These
results suggest that QdO, in particular BPQ and certain derivatives of it, may be useful in protecting the skin against UVB-induced
skin damage. 相似文献
409.
410.
Sonia Barbieri Loretta M. Murphy R. Gary Sawers Robert R. Eady S. Samar Hasnain 《Journal of biological inorganic chemistry》2008,13(4):531-540
We have cloned and expressed the cycP gene encoding cytochrome c′ from Alcaligenes xylosoxidans and generated mutations in Arg-124 and Phe-59, residues close to the haem, to probe their involvement in modulating the unusual
spin-state equilibrium of the haem Fe and the unique proximal mode of binding of NO to form a stable five-coordinate adduct. Arg-124 is located in the proximal pocket of the haem and
forms a hydrogen bond to the stable five-coordinated bound NO. Phe-59 provides steric hindrance at the distal face where NO
binds initially to form a six-coordinate adduct. Optical spectroscopy showed altered electronic properties of the oxidised
haem centre resulting from the mutations of both residues. The high affinity of the ferrous proteins for NO remained unchanged
and all of the mutational variants formed a stable five-coordinate NO species (λ
Soret 395 nm) in the presence of stoichiometric concentrations of NO. However, the kinetics of the reactivity towards NO were altered,
with mutation of the distal Phe-59 residue resulting in the transient six-coordinate distally bound NO adduct (λ
Soret 415 nm) not being detected. Surprisingly, substitution of the proximal residue Arg-124 with Phe, Ala, Gln or Glu also resulted
in the six-coordinate adduct not being detected, showing that this proximal residue also modulates reactivity towards NO on
the opposite haem face. In contrast, the R124L substitution retained the property of the native protein in the initial formation
of a six-coordinate NO adduct, a finding of functional importance since a Lys or an Arg residue is invariant in these proteins. 相似文献