全文获取类型
收费全文 | 644篇 |
免费 | 40篇 |
国内免费 | 2篇 |
出版年
2023年 | 10篇 |
2022年 | 2篇 |
2021年 | 16篇 |
2020年 | 10篇 |
2019年 | 10篇 |
2018年 | 14篇 |
2017年 | 8篇 |
2016年 | 23篇 |
2015年 | 28篇 |
2014年 | 27篇 |
2013年 | 41篇 |
2012年 | 48篇 |
2011年 | 74篇 |
2010年 | 49篇 |
2009年 | 32篇 |
2008年 | 50篇 |
2007年 | 53篇 |
2006年 | 33篇 |
2005年 | 37篇 |
2004年 | 40篇 |
2003年 | 15篇 |
2002年 | 20篇 |
2001年 | 6篇 |
2000年 | 3篇 |
1999年 | 1篇 |
1998年 | 4篇 |
1997年 | 4篇 |
1996年 | 4篇 |
1995年 | 6篇 |
1994年 | 2篇 |
1993年 | 4篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1981年 | 2篇 |
1979年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1963年 | 1篇 |
排序方式: 共有686条查询结果,搜索用时 15 毫秒
121.
Spiliopoulos S Diamantopoulos A Katsanos K Ravazoula P Karnabatidis D Siablis D 《Cryobiology》2011,(3):267-272
Purpose
To in vivo investigate the histological response after single and double cryoplasty therapy in a rabbit iliac artery model.Materials and methods
In total, 40 New Zealand White rabbits underwent percutaneous transluminal angioplasty of the iliac artery using either PolarCath balloon or a conventional angioplasty balloon of equal diameter. Arterial injury, inflammatory response and smooth muscle cells (SMC) apoptosis with the TUNEL (Terminal deoxynucleotidyl transferase dUTP Nick End Labeling) immunohistochemical assay were analyzed. Rabbits were divided between single or double balloon inflation and histological results were compared between cryoplasty and control angioplasty both at 30 min and 72 h.Results
Arterial injury and wall inflammation scores were low and similar between cryoplasty and control groups after single and double balloon inflation. Compared to conventional balloon angioplasty, Polarcath cryoplasty demonstrated superior SMC apoptosis after single inflation at 30 min [12.0 ± 1.2 cells/(0.025 mm)2 vs 7.0 ± 1.5 cells/(0.025 mm)2, p = 0.002], single inflation at 72 h [9.0 ± 1.0 cells/(0.025 mm)2 vs 5.4 ± 1.4 cells/(0.025 mm)2, p = 0.001], double inflation at 30 min [11.6 ± 1.5 cells/(0.025 mm)2 vs 6.8 ± 1.4 cells/(0.025 mm)2, p = 0.001] and double inflation at 72 h [9.2 ± 0.8 cells/(0.025 mm)2 vs 5.0 ± 0.7 cells/(0.025 mm)2, p = 0.001]. There were no significant differences in apoptosis between single and double cryoplasty application at 30 min and 72 h.Conclusion
Cryoplasty demonstrated superior rates of SMC apoptosis at 30 min and 72 h and was associated to relatively low arterial injury and inflammation scores. An immediate second PolarCath inflation did not achieve superior apoptosis. 相似文献122.
Nichols RJ Sen S Choo YJ Beltrao P Zietek M Chaba R Lee S Kazmierczak KM Lee KJ Wong A Shales M Lovett S Winkler ME Krogan NJ Typas A Gross CA 《Cell》2011,144(1):143-156
The explosion of sequence information in bacteria makes developing high-throughput, cost-effective approaches to matching genes with phenotypes imperative. Using E. coli as proof of principle, we show that combining large-scale chemical genomics with quantitative fitness measurements provides a high-quality data set rich in discovery. Probing growth profiles of a mutant library in hundreds of conditions in parallel yielded > 10,000 phenotypes that allowed us to study gene essentiality, discover leads for gene function and drug action, and understand higher-order organization of the bacterial chromosome. We highlight new information derived from the study, including insights into a gene involved in multiple antibiotic resistance and the synergy between a broadly used combinatory antibiotic therapy, trimethoprim and sulfonamides. This data set, publicly available at http://ecoliwiki.net/tools/chemgen/, is a valuable resource for both the microbiological and bioinformatic communities, as it provides high-confidence associations between hundreds of annotated and uncharacterized genes as well as inferences about the mode of action of several poorly understood drugs. 相似文献
123.
The N-methyl-D-aspartate receptor (NMDAR) is a key molecule mediating brain plasticity related processes. Knowing that alternative splicing
of the NMDAR1 (NR1) subunit offers molecular diversity to NMDAR, controls the forward trafficking of the NR1 protein and is
important for placing NMDA receptors at synapses, we investigated herein the postnatal developmental expression and the influence
of visual deprivation on NR1 subunit splice variants in rat retina. Real-time PCR was performed using oligonucleotide primers
specific for N- terminal (NR1a, NR1b) and C-terminal splice variants (NR1-1, NR1-2, NR1-3, NR1-4). The developmental profiles
of mRNA expression levels of all NR1 isoforms peaked at the end of the third week. Dark rearing led to reductions in both
N- and C-terminal NR1 variants in several developmental ages and a significant interaction between age and visual experience
was observed for NR1a, NR1-2 and NR1-4 expression. Our results have demonstrated a developmental and visual experience-dependent
regulation of NR1 splicing in rat retina. 相似文献
124.
Skyrianou KC Perdih F Papadopoulos AN Turel I Kessissoglou DP Psomas G 《Journal of inorganic biochemistry》2011,105(10):1273-1285
The nickel(II) complexes with the quinolone antibacterial agents oxolinic acid, flumequine, enrofloxacin and sparfloxacin in the presence of the N,N′-donor heterocyclic ligand 2,2′-bipyridylamine have been synthesized and characterized. The quinolones act as bidentate ligands coordinated to Ni(II) ion through the pyridone oxygen and a carboxylato oxygen. The crystal structure of [(2,2′-bipyridylamine)bis(sparfloxacinato)nickel(II)] has been determined by X-ray crystallography. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that they bind to CT DNA with [(2,2′-bipyridylamine)bis(flumequinato)nickel(II)] exhibiting the highest binding constant to CT DNA. The cyclic voltammograms of the complexes have shown that in the presence of CT DNA the complexes can bind to CT DNA by the intercalative binding mode which has also been verified by DNA solution viscosity measurements. Competitive study with ethidium bromide (EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB. The complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values. The biological properties of the [Ni(quinolonato)2(2,2′-bipyridylamine)] complexes have been evaluated in comparison to the previously reported Ni(II) quinolone complexes [Ni(quinolonato)2(H2O)2], [Ni(quinolonato)2(2,2′-bipyridine)] and [Ni(quinolonato)2(1,10-phenanthroline)]. The quinolones and their Ni(II) complexes have been tested for their antioxidant and free radical scavenging activity. They have been also tested in vitro for their inhibitory activity against soybean lipoxygenase. 相似文献
125.
126.
127.
Martha Stathaki Athanasios Armakolas Andreas Dimakakos Loukas Kaklamanis Ioannis Vlachos Manoussos M Konstantoulakis George Zografos Michael Koutsilieris 《Molecular medicine (Cambridge, Mass.)》2014,20(1):80-92
Kisspeptin is an antimetastatic agent in some cancers that has also been associated with lymphoid cell apoptosis, a phenomenon favoring metastases. Our aim was to determine the association of kisspeptin with lymphocyte apoptosis and the presence of metastases in colorectal cancer patients. Blood was drawn from 69 colon cancer patients and 20 healthy volunteers. Tissue specimens from healthy and pathological tissue were immunohistochemically analyzed for kisspeptin and endothelial monocyte activating polypeptide II (EMAP-II) expression. Blood EMAP-II and soluble Fas ligand (sFasL) levels were examined by an enzyme-linked immunosorbent assay method. The kisspeptin and EMAP-II expression and secretion levels in the DLD-1 and HT-29 colon cancer cell lines were examined by quantitative real-time polymerase chain reaction, Western analysis and enzyme-linked immunosorbent assay, whereas lymphocyte viability was assessed by flow cytometry. The effect of kisspeptin on the viability of colon cancer cells was examined by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]. Exogenous, synthetic and naturally produced, kisspeptin induces through the G-protein-coupled receptor 54 (GPR54; also known as the kisspeptin receptor) the EMAP-II expression and secretion in colon cancer cell lines, inducing in vitro lymphocyte apoptosis, as verified by the use of an anti-EMAP-II antibody. These results were reversed with the use of kisspeptin inhibitors and by kisspeptin-silencing experiments. Tumor kisspeptin expression was associated with the tumor EMAP-II expression (p < 0.001). Elevated kisspeptin and EMAP-II expression in colon cancer tissues was associated with lack of metastases (p < 0.001) in colon cancer patients. These data indicate the antimetastatic effect of tumor-elevated kisspeptin in colon cancer patients that may be mediated by the effect of kisspeptin on EMAP-II expression in colon cancer tumors in patients with normal serum EMAP-II levels. These findings provide new insight into the role of kisspeptin in the context of metastases in colon cancer patients. 相似文献
128.
Margherita Rosati Mahesh Agarwal Xintao Hu Santhi Devasundaram Dimitris Stellas Bhabadeb Chowdhury Jenifer Bear Robert Burns Duncan Donohue Laurent Pessaint Hanne Andersen Mark G. Lewis Evangelos Terpos Meletios Athanasios Dimopoulos Alexander Wlodawer James I. Mullins David J. Venzon George N. Pavlakis Barbara K. Felber 《PLoS pathogens》2021,17(9)
The speed of development, versatility and efficacy of mRNA-based vaccines have been amply demonstrated in the case of SARS-CoV-2. DNA vaccines represent an important alternative since they induce both humoral and cellular immune responses in animal models and in human trials. We tested the immunogenicity and protective efficacy of DNA-based vaccine regimens expressing different prefusion-stabilized Wuhan-Hu-1 SARS-CoV-2 Spike antigens upon intramuscular injection followed by electroporation in rhesus macaques. Different Spike DNA vaccine regimens induced antibodies that potently neutralized SARS-CoV-2 in vitro and elicited robust T cell responses. The antibodies recognized and potently neutralized a panel of different Spike variants including Alpha, Delta, Epsilon, Eta and A.23.1, but to a lesser extent Beta and Gamma. The DNA-only vaccine regimens were compared to a regimen that included co-immunization of Spike DNA and protein in the same anatomical site, the latter of which showed significant higher antibody responses. All vaccine regimens led to control of SARS-CoV-2 intranasal/intratracheal challenge and absence of virus dissemination to the lower respiratory tract. Vaccine-induced binding and neutralizing antibody titers and antibody-dependent cellular phagocytosis inversely correlated with transient virus levels in the nasal mucosa. Importantly, the Spike DNA+Protein co-immunization regimen induced the highest binding and neutralizing antibodies and showed the strongest control against SARS-CoV-2 challenge in rhesus macaques. 相似文献
129.
Michael Karpusas Irine Axarli Lykourgos Chiniadis Athanasios Papakyriakou Kostas Bethanis Katholiki Scopelitou Yannis D. Clonis Nikolaos E. Labrou 《PloS one》2013,8(2)
Glutathione transferases (GSTs) are enzymes that contribute to cellular detoxification by catalysing the nucleophilic attack of glutathione (GSH) on the electrophilic centre of a number of xenobiotic compounds, including several chemotherapeutic drugs. In the present work we investigated the interaction of the chemotherapeutic drug chlorambucil (CBL) with human GSTA1-1 (hGSTA1-1) using kinetic analysis, protein crystallography and molecular dynamics. In the presence of GSH, CBL behaves as an efficient substrate for hGSTA1-1. The rate-limiting step of the catalytic reaction between CBL and GSH is viscosity-dependent and kinetic data suggest that product release is rate-limiting. The crystal structure of the hGSTA1-1/CBL-GSH complex was solved at 2.1 Å resolution by molecular replacement. CBL is bound at the H-site attached to the thiol group of GSH, is partially ordered and exposed to the solvent, making specific interactions with the enzyme. Molecular dynamics simulations based on the crystal structure indicated high mobility of the CBL moiety and stabilization of the C-terminal helix due to the presence of the adduct. In the absence of GSH, CBL is shown to be an alkylating irreversible inhibitor for hGSTA1-1. Inactivation of the enzyme by CBL followed a biphasic pseudo-first-order saturation kinetics with approximately 1 mol of CBL per mol of dimeric enzyme being incorporated. Structural analysis suggested that the modifying residue is Cys112 which is located at the entrance of the H-site. The results are indicative of a structural communication between the subunits on the basis of mutually exclusive modification of Cys112, indicating that the two enzyme active sites are presumably coordinated. 相似文献
130.
Demetrio Tamiolakis John Venizelos Maria Lambropoulou Silva Nikolaidou Sophia Bolioti Maria Tsiapali Dionysios Verettas Panagiotis Tsikouras Athanasios Chatzimichail Nikolas Papadopoulos 《Theoretical biology & medical modelling》2005,2(1):1