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931.
Tatjana P. Stanojkovic Alexandra Primikyri Alfonso Castineiras Mavroudis A. Demertzis 《Journal of inorganic biochemistry》2010,104(4):467-10884
2-Acetyl pyridine thiosemicarbazone containing an 1-(4-fluorophenyl)-piperazinyl ring incorporated at N(4)-position, HAcPipPheF (1) and the zinc(II) complexes [Zn(AcPipPheF)2] (2) and [Zn(OAc)(AcPipPheF)]2 (3) have been prepared and structurally characterized by means of vibrational and NMR (1H and 13C) spectroscopy. The crystal structures of the compounds 1-3 have been determined by X-ray crystallography. The metal coordination geometry of [Zn(AcPipPheF)2] is described as distorted octahedral configuration in a trans-N-cis-N-cis-S configuration. In [Zn(OAc)(AcPipPheF)]2 one of the acetato group exhibits monoatomic bridge and the other bridges in a bidentate manner. The zinc(1) metal ion is coordinated in a distorted octahedral configuration while the metal coordination of Zn(2) is described as distorted square pyramidal. Biomedical studies revealed that, compounds 1-3 displayed potent anticancer activity. The antiproliferative activity of 1-3 was found to be considerably stronger than that of cis-platin. The IC50 values range from 26 to 90 nM, against all cell lines tested, while for cis-platin the IC50 values range from 2 to 17 μM and for the zinc salt, ZnCl2, the IC50 values range from 81 to 93 μM. The complex 3 shows the highest activity against all four cancer cell lines and the highest selectivity against K562 and MDA-MB-453 cancer cell lines. The compounds inhibited tumor cell proliferation by arresting the cell cycle progression at the S phase. 相似文献
932.
Aline Lara Denis D. Damasceno Rita Pires Robert Gros Enéas R. Gomes Mariana Gavioli Ricardo F. Lima Diogo Guimar?es Patricia Lima Carlos Roberto Bueno Jr. Anilton Vasconcelos Danilo Roman-Campos Cristiane A. S. Menezes Raquel A. Sirvente Vera M. Salemi Charles Mady Marc G. Caron Anderson J. Ferreira Patricia C. Brum Rodrigo R. Resende Jader S. Cruz Marcus Vinicius Gomez Vania F. Prado Alvair P. de Almeida Marco A. M. Prado Silvia Guatimosim 《Molecular and cellular biology》2010,30(7):1746-1756
933.
Cláudia Funchal Carlos Augusto Souza Carvalho Tanise Gemelli Andressa S. Centeno Robson Brum Guerra Mirian Salvador Caroline Dani Adriana Coitinho Rosane Gomez 《Cellular and molecular neurobiology》2010,30(7):1135-1142
Organotellurium compounds have been synthesized since 1840, but pharmacological and toxicological studies about them are still
incipient. Therefore, the objective of this study was to verify the effect of acute administration of the organochalcogen
3-butyl-1-phenyl-2-(phenyltelluro)oct-en-1-one on some parameters of oxidative stress in the brain of 30-day-old rats. Animals
were treated intraperitoneally with a single dose of the organotellurium (125, 250, or 500 μg/kg body weight) and sacrificed
60 min after the injection. The cerebral cortex, the hippocampus, and the cerebellum were dissected and homogenized in KCl.
Afterward, thiobarbituric acid reactive substances (TBARS), carbonyl, sulfhydryl, catalase (CAT), superoxide dismutase (SOD),
nitric oxide (NO) formation, and hydroxyl radical production were measured in the brain. The organotellurium enhanced TBARS
in the cerebral cortex and the hippocampus, and increased protein damage (carbonyl) in the cerebral cortex and the cerebellum.
In contrast, the compound provoked a reduced loss of thiol groups measured by the sulfhydryl assay in all the tissues studied.
Furthermore, the activity of the antioxidant enzyme CAT was reduced by the organochalcogen in the cerebral cortex and the
cerebellum, and the activity of SOD was inhibited in all the brain tissues. Moreover, NO production was increased in the cerebral
cortex and the cerebellum by this organochalcogen, and hydroxyl radical formation was also enhanced in the cerebral cortex.
Our findings indicate that this organotellurium compound induces oxidative stress in the brain of rats, corroborating that
this tissue is a potential target for organochalcogen action. 相似文献
934.
Biava M Porretta GC Poce G Battilocchio C Alfonso S De Logu A Serra N Manetti F Botta M 《Bioorganic & medicinal chemistry》2010,18(22):8076-8084
A hit optimization procedure based on isosteric and bioisosteric replacement of decorating groups at both the N1 and the C5 phenyl rings of 1,5-diarylpyrroles led to identification of 4-((1-(4-fluorophenyl)-2-methyl-5-(4-(methylthio)phenyl)-1H-pyrrol-3-yl)methyl)thiomorpholine that is characterized by a very high activity toward both Mycobacterium tuberculosis 103471 and H37Rv strains (MIC values of 0.125μg/mL), and a safe profile in terms of cytotoxicity (CC(50) of >128μg/mL) and protection index (>1000). Antitubercular activity and protection index of the new compound are comparable to those found for the current antitubercular drugs streptomycin and rifampin. 相似文献
935.
Luca Mologni Roberta Rostagno Stefania Brussolo Phillip P. Knowles Svend Kjaer Judith Murray-Rust Enrico Rosso Alfonso Zambon Leonardo Scapozza Neil Q. McDonald Vittorio Lucchini Carlo Gambacorti-Passerini 《Bioorganic & medicinal chemistry》2010,18(4):1482-1496
The synthesis, structure–activity relationships (SAR) and structural data of a series of indolin-2-one inhibitors of RET tyrosine kinase are described. These compounds were designed to explore the available space around the indolinone scaffold within RET active site. Several substitutions at different positions were tested and biochemical data were used to draw a molecular model of steric and electrostatic interactions, which can be applied to design more potent and selective RET inhibitors. The crystal structures of RET kinase domain in complex with three inhibitors were solved. All three compounds bound in the ATP pocket and formed two hydrogen bonds with the kinase hinge region. Crystallographic analysis confirmed predictions from molecular modelling and helped refine SAR results. These data provide important information for the development of indolinone inhibitors for the treatment of RET-driven cancers. 相似文献
936.
Maria Luisa Balestrieri Alfonso GiovaneLara Milone Luigi Servillo 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2010,1801(10):1123-1132
Endothelial progenitor cell (EPC) therapy is a promising approach to promote angiogenesis and endothelial repair in patients with cardiovascular diseases (CVD). However, their release of proinflammatory mediators may compromise the therapeutic efficacy. Little is known about the role of Platelet-Activating Factor (PAF) in EPC functional response. Here, we investigated the expression of PAF receptor (PAF-R) in early EPC and the release of PAF under stimulation with factors involved in endothelial dysfunction. Results indicated that early EPC express the PAF-R and respond to PAF signaling via a transient increase of cytoplasmic Ca2+ concentration. EPC release PAF in a time dependent manner upon stimulation with tumor necrosis factor-α (TNF-α) or high-glucose concentration with a peak at 30 min and 10 min (p < 0.01 vs. control), respectively. PAF, starting at concentration of 50 ng/ml, exerted a detrimental effect on EPC number with a concomitant increase of p38 activity. Furthermore, both the reduction of early EPC number and the enhanced p38 activity induced by PAF were abolished by CV3988, a PAF receptor antagonist. These novel findings, revealing that early EPC respond to PAF signaling, unveil an inflammatory pathway that may play a crucial role in the outcome of cardiovascular cell therapy with EPC. 相似文献
937.
Kevin M Curtis Lourdes A Gomez Carmen Rios Elisa Garbayo Ami P Raval Miguel A Perez-Pinzon Paul C Schiller 《BMC molecular biology》2010,11(1):61
Background
RT-qPCR analysis is a widely used method for the analysis of mRNA expression throughout the field of mesenchymal stromal cell (MSC) research. Comparison between MSC studies, both in vitro and in vivo, are challenging due to the varied methods of RT-qPCR data normalization and analysis. Therefore, this study focuses on putative housekeeping genes for the normalization of RT-qPCR data between heterogeneous commercially available human MSC, compared with more homogeneous populations of MSC such as MIAMI and RS-1 cells. 相似文献938.
Tom T. Chen Alfonso Luque Sunyoung Lee Sean M. Anderson Tatiana Segura M. Luisa Iruela-Arispe 《The Journal of cell biology》2010,188(4):595-609
VEGF can be secreted in multiple isoforms with variable affinity for extracellular proteins and different abilities to induce vascular morphogenesis, but the molecular mechanisms behind these effects remain unclear. Here, we show molecular distinctions between signaling initiated from soluble versus matrix-bound VEGF, which mediates a sustained level of VEGFR2 internalization and clustering. Exposure of endothelial cells to matrix-bound VEGF elicits prolonged activation of VEGFR2 with differential phosphorylation of Y1214, and extended activation kinetics of p38. These events require association of VEGFR2 with β1 integrins. Matrix-bound VEGF also promotes reciprocal responses on β1 integrin by inducing its association with focal adhesions; a response that is absent upon exposure to soluble VEGF. Inactivation of β1 integrin blocks the prolonged phosphorylation of Y1214 and consequent activation of p38. Combined, these results indicate that when in the context of extracellular matrix, activation of VEGFR2 is distinct from that of soluble VEGF in terms of recruitment of receptor partners, phosphorylation kinetics, and activation of downstream effectors. 相似文献
939.
José R. Pedrajas Alfonso Carreras Raquel Valderrama Juan B. Barroso 《Nitric oxide》2010,22(3):206-213
Peroxynitrite is a reactive nitrogen species that can mediate protein tyrosine nitration, inactivating many proteins. We show that yeast mitochondrial peroxiredoxin (Prx1p), which belongs to the group 1-Cys-Prx, has thioredoxin-dependent peroxynitrite reductase activity. This activity was characterised in vitro with the recombinant mitochondrial Prx1p, the thioredoxin reductase Trr2p and the thioredoxin Trx3p, using a generator of peroxynitrite (SIN-1). Purified mitochondria from wild-type and null Prx1p or Trx3p yeast strains, exposed to SIN-1, showed a differential inactivation of manganese-containing superoxide dismutase activity. The above yeast strains were exposed to SIN-1 and examined under confocal microscopy. Prx1p or Trx3p-null cells showed a greater accumulation of peroxynitrite than wild-type ones. Our results indicate that this 1-Cys-Prx is a peroxynitrite reductase activity that uses reducing equivalents from NADPH through the mitochondrial thioredoxin system. Therefore, mitochondrial 1-Cys-peroxiredoxin/thioredoxin system constitutes an essential antioxidant defence against oxidative and nitrosative stress in yeast mitochondria. 相似文献
940.
Claudia Alfonso Mónica López Alicia Arechavala María del Carmen Perrone Liliana Guelfand Mario Bianchi 《Revista iberoamericana de micología》2010,27(2):90-93
Fungal infections caused by yeasts have increased during the last decades and invasive forms represent a serious problem for human health. Candida albicans is the species most frequently isolated from clinical samples. However, other emerging yeast pathogens are increasingly responsible for mycotic infections, and some of them are resistant to some antifungal drugs. Consequently, it is necessary to have methods that can provide a rapid presumptive identification at species level.Numerous chromogenic agar media have been shown to be of value as diagnostic tools. We have compared a chromogenic medium, Brilliance Candida Agar, with CHROMagar Candida, the chromogenic medium most used in our country. A multicentre study was conducted in 16 Hospitals belonging to the Mycology Net of Buenos Aires City Government. A total of 240 yeast isolates were included in this research.The new chromogenic agar showed results very similar to those obtained with CHROMagar Candida. 相似文献