全文获取类型
收费全文 | 988篇 |
免费 | 121篇 |
出版年
2023年 | 1篇 |
2022年 | 5篇 |
2021年 | 17篇 |
2020年 | 16篇 |
2019年 | 17篇 |
2018年 | 19篇 |
2017年 | 25篇 |
2016年 | 22篇 |
2015年 | 29篇 |
2014年 | 36篇 |
2013年 | 44篇 |
2012年 | 73篇 |
2011年 | 66篇 |
2010年 | 45篇 |
2009年 | 50篇 |
2008年 | 58篇 |
2007年 | 54篇 |
2006年 | 51篇 |
2005年 | 44篇 |
2004年 | 45篇 |
2003年 | 48篇 |
2002年 | 30篇 |
2001年 | 36篇 |
2000年 | 41篇 |
1999年 | 24篇 |
1998年 | 14篇 |
1997年 | 14篇 |
1996年 | 16篇 |
1995年 | 8篇 |
1994年 | 12篇 |
1993年 | 12篇 |
1992年 | 17篇 |
1991年 | 13篇 |
1990年 | 9篇 |
1989年 | 6篇 |
1988年 | 9篇 |
1987年 | 14篇 |
1986年 | 13篇 |
1985年 | 12篇 |
1984年 | 3篇 |
1983年 | 5篇 |
1982年 | 3篇 |
1981年 | 8篇 |
1980年 | 4篇 |
1979年 | 7篇 |
1978年 | 4篇 |
1976年 | 3篇 |
1975年 | 4篇 |
1973年 | 2篇 |
1969年 | 1篇 |
排序方式: 共有1109条查询结果,搜索用时 15 毫秒
101.
102.
Prieto P Moore G Reader S 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2005,111(3):505-510
During early meiosis, chromosomes pair via their telomeres and centromeres. This pairing induces a conformational change which propagates from these regions along each chromosome, making the chromatin of the partners accessible for intimate pairing. In the present study, we show by exploiting wheat–rye hybrids that the signal is initiated in both the presence and absence of either the Ph1 or Ph2 locus. However, the chromatin change only continues to propagate through rye telomeric heterochromatin when Ph1 is absent. This failure to propagate the chromatin change through the rye heterochromatin in the absence of Ph2 correlates with a subsequent lack of wheat–rye chromosome association at metaphase I. 相似文献
103.
In spite of its widespread use, benznidazole's (BNZ) toxicity and low efficacy remains as major drawbacks that impair successful treatments against Chagas disease. Previously, attempting to increase the selectivity and reduce its toxicity on infected tissues, multilamellar liposomes (MLV) composed of hydrogenated soybean phosphatidylcholine (HSPC): distearoyl-phosphatidylglycerol (DSPG): cholesterol (CHOL) 2:1:2 mol:mol loaded with BNZ (MLV-BNZ) were designed. In this work we compared different properties of MLV-BNZ with those of BNZ. Opposite to other hydrophobic drugs, the results indicated that slight changes of BNZ's association degree to proteins and lipoproteins should not modify the percentage of unbound drug available to exert pharmacological action. On the other hand, when loaded in MLV, BNZ reduced its association to plasma proteins in 45% and became refractory to the sinking effect of blood, dropping 4.5 folds. Additionally, when loaded in MLV, BNZ had higher volume distribution (160 +/- 20 vs 102 +/- 15 ml/kg) and total clearance (35.23 +/- 2.3 vs 21.9 +/- 1.4 ml/h.kg), and lower concentration-time curve (7.23 +/- 0.2 vs 9.16 +/- 0.5 microg.h/ml) than BNZ. Hence, these studies showed that for MLV-BNZ, the amount of BNZ can be substantially increased, from 25 to 70%, being this formulation more rapidly cleared from circulation than free drug; also due to the lower interaction with blood components, lower side effects can be expected. 相似文献
104.
Balseiro A Espí A Márquez I Pérez V Ferreras MC Marín JF Prieto JM 《Journal of wildlife diseases》2005,41(2):371-378
A total of 2,465 seabirds, mainly common murres (Uria aalge), razorbills (Alca torda), and puffins (Fratercula arctica) that beached in the northwestern part of Spain after the "Prestige" oil spill on 19 November 2002 were examined by pathological methods. Birds were divided into three groups: dead birds with the body covered (group 1) or uncovered (group 2) by oil and birds recovered alive but which died after being treated at a rescue center (group 3). The main gross lesions were severe dehydration and emaciation. Microscopically, hemosiderin deposits, related to cachexia and/or hemolytic anemia, were observed in those birds harboring oil in the intestine. Severe aspergillosis and ulcers in the ventriculus were found only in group 3 birds, probably because of stress associated with attempted rehabilitation at the rescue center. The mild character of the pathological changes suggests that petroleum oil toxicosis causes multiple sublethal changes that have an effect on the ability of the birds to survive at sea, especially weak and young, inexperienced animals. Dehydration and exhaustion seem to be the most likely cause of death. 相似文献
105.
Prieto JG Pulido MM Zapico J Molina AJ Gimeno M Coronel P Alvarez AI 《International journal of biological macromolecules》2005,35(1-2):63-69
Depolymerisation by oxytetracycline (OTC) as well as the progressive cleavage of hyaluronic acid induced by ultrasound was investigated in nine commercially available hyaluronic polymers. Sample solutions differed in molecular weight, from 500 to 7000 kDa, and in their source. The hyaluronic acid concentration in each sample was analysed by HPLC. The concentration range was over 8.39-10.18 mg ml(-1) in samples with a nominal concentration of 1%, and 14.05 mg ml(-1) in one sample with a nominal concentration of 1.5%. It was found that stability was dependent on both molecular weight and the concentration of the samples. The rheological parameters n (power law index) and K (consistency coefficient) were good predictors regarding the degradation behaviour. Although many factors are involved in obtaining a therapeutic response, the results obtained in this work support the notion that both mechanical and chemical degradation are reduced in hyaluronate solutions with low molecular weight, the final concentration of the product being a critical factor. 相似文献
106.
Sarciron ME Terreux R Prieto Y Cortes M Cuellar MA Tapia RA Domard M Walchshofer N Pétavy AF 《Parasite (Paris, France)》2005,12(3):251-258
33 polycyclic derivatives have been studied and tested on Leishmania donovani and L. major promastigotes. Their antileishmanial activity was assessed in vitro and an assay of their cytotoxicity was realized on human myelomonocytic cell line. The reference molecules used in the assays were amphotericin B and pentamidine. Among the compounds tested, 29 possess an antileishmanial activity; 25 of those were more active against L. donovani than amphotericin B, and nine were as effective as amphotericin B against L. major. Many synthesized derivatives were more active against L. donovani than against L. major. The cytotoxicity studies have shown that among the thirty-three derivatives tested, 12 molecules have an IC50 towards THP-1 cells about equal than that reference drugs, the 21 other derivatives are much less toxic. A 3D QSAR study was undertaken and has permitted to predict activity against L. donovani and L. major and to highlight critical area to optimize activity against the two species. 相似文献
107.
Smith BM Smith JM Tsai JH Schultz JA Gilson CA Estrada SA Chen RR Park DM Prieto EB Gallardo CS Sengupta D Thomsen WJ Saldana HR Whelan KT Menzaghi F Webb RR Beeley NR 《Bioorganic & medicinal chemistry letters》2005,15(5):1467-1470
We report on the synthesis, biological evaluation and structure-activity relationships for a series of 3-benzazepine derivatives as 5-HT(2C) receptor agonists. The compounds were evaluated in functional assays measuring [3H] phosphoinositol turnover in HEK-293 cells transiently transfected with h5-HT(2C), h5-HT(2A) or h5-HT(2B) receptors. Several compounds are shown to be potent and selective 5-HT(2C) receptor agonists, which decrease food intake in a rat feeding model. 相似文献
108.
Martín JA Brooks DA Prieto L González R Torrado A Rojo I López de Uralde B Lamas C Ferritto R Dolores Martín-Ortega M Agejas J Parra F Rizzo JR Rhodes GA Robey RL Alt CA Wendel SR Zhang TY Reifel-Miller A Montrose-Rafizadeh C Brozinick JT Hawkins E Misener EA Briere DA Ardecky R Fraser JD Warshawsky AM 《Bioorganic & medicinal chemistry letters》2005,15(1):51-55
Herein we describe a series of potent and selective PPARgamma agonists with moderate PPARalpha affinity and little to no affinity for other nuclear receptors. In vivo studies in a NIDDM animal model (ZDF rat) showed that these compounds are efficacious at low doses in glucose normalization and plasma triglyceride reduction. Compound 1b (LY519818) was selected from our SAR studies to be advanced to clinical evaluation for the treatment of type II diabetes. 相似文献
109.
Novel role for amphiregulin in protection from liver injury 总被引:2,自引:0,他引:2
Berasain C García-Trevijano ER Castillo J Erroba E Santamaría M Lee DC Prieto J Avila MA 《The Journal of biological chemistry》2005,280(19):19012-19020
110.
Identification and quantitation of species in complex DNA mixtures by real-time polymerase chain reaction 总被引:10,自引:0,他引:10
López-Andreo M Lugo L Garrido-Pertierra A Prieto MI Puyet A 《Analytical biochemistry》2005,339(1):73-82
Six TaqMan real-time polymerase chain reaction (PCR) systems using minor groove binding (MGB) probes have been developed for the detection quantitation of bovine, porcine, lamb, chicken, turkey, and ostrich DNA in complex samples. Species-specific amplification was achieved by combining only two fluorogenic probes and 10 oligonucleotide primers targeting mitochondrial sequences, decreasing the cost of the assay significantly. The limits of detection ranged from 0.03 to 0.80 pg of template DNA. Analysis of experimental mixtures containing two to four different species showed the suitability of the assay for detection of more than 1% of pork, chicken, or turkey and of more than 5% of cattle or lamb. The quantitation accuracy in samples containing 10-100% of beef or pork DNA was close to 90%. The system is complemented with one additional TaqMan MGB detector based on consensus sequence segments of the nuclear 18S ribosomal RNA gene. A method to evaluate the presence of unknown eukaryotic DNA in a mixture, where data derived from the species-specific detection are compared with the experimental values obtained from the general 18S detector, is presented. This method allows the validation of the quantitative measurements, providing an internal control of the total content of PCR-amplifiable DNA in the sample. The system was tested on DNA mixtures containing different shares of up to four different species and on DNA extracted from processed commercial food samples. 相似文献