全文获取类型
收费全文 | 1916篇 |
免费 | 125篇 |
国内免费 | 2篇 |
出版年
2023年 | 13篇 |
2022年 | 24篇 |
2021年 | 45篇 |
2020年 | 45篇 |
2019年 | 56篇 |
2018年 | 74篇 |
2017年 | 58篇 |
2016年 | 79篇 |
2015年 | 120篇 |
2014年 | 108篇 |
2013年 | 119篇 |
2012年 | 160篇 |
2011年 | 151篇 |
2010年 | 90篇 |
2009年 | 87篇 |
2008年 | 103篇 |
2007年 | 84篇 |
2006年 | 100篇 |
2005年 | 53篇 |
2004年 | 66篇 |
2003年 | 58篇 |
2002年 | 44篇 |
2001年 | 38篇 |
2000年 | 31篇 |
1999年 | 17篇 |
1998年 | 10篇 |
1997年 | 15篇 |
1996年 | 9篇 |
1995年 | 10篇 |
1994年 | 9篇 |
1993年 | 7篇 |
1992年 | 14篇 |
1991年 | 13篇 |
1990年 | 11篇 |
1989年 | 16篇 |
1988年 | 6篇 |
1987年 | 8篇 |
1986年 | 8篇 |
1985年 | 7篇 |
1984年 | 4篇 |
1983年 | 4篇 |
1981年 | 7篇 |
1980年 | 5篇 |
1979年 | 9篇 |
1978年 | 5篇 |
1977年 | 7篇 |
1976年 | 6篇 |
1975年 | 4篇 |
1974年 | 4篇 |
1967年 | 4篇 |
排序方式: 共有2043条查询结果,搜索用时 31 毫秒
991.
Walciane da Silva Maria das Graças Machado Freire José Roberto Postali Parra Sergio Marangoni Maria Lígia Rodrigues Macedo 《Process Biochemistry》2012,47(2):257-263
Diatraea saccharalis, is a major sugarcane pest, causing damage to the stalks of sugarcane plants. In this study, a trypsin inhibitor (ApTI) was purified from Adenanthera pavonina seeds and was tested for its insect growth regulatory effect. ApTI showed a dose-dependent effect on average larval weight and survival. 0.1% ApTI produced approximately 67% and 50% decreases in weight and survival larval, respectively. The results from dietary utilization experiments with D. saccharalis larvae showed a reduction in the efficiency of conversion of ingested food and digested food, and an increase in approximate digestibility and metabolic cost. The level of trypsin was significantly decreased (ca. 55%) in the midgut of larvae reared on a diet containing 0.05% ApTI and the trypsin activity in ApTI-fed larvae demonstrated sensitivity to ApTI. The action of ApTI on the development of D. saccharalis larvae shows that this protein may have great toxic potential. 相似文献
992.
Alessandra Machado Marcos A. Fázio Antonio Miranda Sirlei Daffre M. Teresa Machini 《Journal of peptide science》2012,18(9):588-598
Gomesin (Gm) was the first antimicrobial peptide (AMP) isolated from the hemocytes of a spider, the Brazilian mygalomorph Acanthoscurria gomesiana. We have been studying the properties of this interesting AMP, which also displays anticancer, antimalarial, anticryptococcal and anti‐Leishmania activities. In the present study, the total syntheses of backbone‐cyclized analogues of Gm (two disulfide bonds), [Cys(Acm)2,15]‐Gm (one disulfide bond) and [Thr2,6,11,15,d ‐Pro9]‐Gm (no disulfide bonds) were accomplished, and the impact of cyclization on their properties was examined. The consequence of simultaneous deletion of pGlu1 and Arg16‐Glu‐Arg18‐NH2 on Gm antimicrobial activity and structure was also analyzed. The results obtained showed that the synthetic route that includes peptide backbone cyclization on resin was advantageous and that a combination of 20% DMSO/NMP, EDC/HOBt, 60 °C and conventional heating appears to be particularly suitable for backbone cyclization of bioactive peptides. The biological properties of the Gm analogues clearly revealed that the N‐terminal amino acid pGlu1 and the amidated C‐terminal tripeptide Arg16‐Glu‐Arg18‐NH2 play a major role in the interaction of Gm with the target membranes. Moreover, backbone cyclization practically did not affect the stability of the peptides in human serum; it also did not affect or enhanced hemolytic activity, but induced selectivity and, in some cases, discrete enhancements of antimicrobial activity and salt tolerance. Because of its high therapeutic index, easy synthesis and lower cost, the [Thr2,6,11,15,d ‐Pro9]‐Gm analogue remains the best active Gm‐derived AMP developed so far; nevertheless, its elevated instability in human serum may limit its therapeutic potential. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
993.
de Castro UG de Sousa GG Machado Rdo P Isoldi MC Silva ME Nadu AP Sousa LE Santos RA Campagnole-Santos MJ Alzamora AC 《Nitric oxide》2012,26(2):118-125
Hypertension is associated to an increase in central oxidative stress and an attenuation of the baroreflex control of arterial pressure. The present study evaluated the effect of alterations in the levels of nitric oxide (NO) and superoxide anion in the caudal ventrolateral medulla (CVLM), a key area of the brainstem for the baroreflex control of arterial pressure, in renovascular hypertensive rats (2K1C). Baseline mean arterial pressure (MAP), heart rate (HR), and reflex bradycardia were evaluated 30 days after renal artery occlusion in anesthetized (urethane, 1.2 g/kg, i.p.) 2K1C or normotensive (SHAM) rats. The MAP, HR, and baroreflex control of HR were evaluated before and after CVLM microinjections of the non-selective NOS inhibitor L-NAME (10 nmol), the NO precursor L-ARG (50 nmol), or the antioxidant ascorbic acid, Vit C (10 nmol). In both 2K1C and SHAM animals, CVLM microinjection of L-NAME produced a decrease in MAP, whereas L-ARG induced a significant increase in MAP. However, microinjection of Vit C into the CVLM produced a decrease in MAP and HR only in 2K1C and not in SHAM rats. Cardiovascular effects produced by microinjection of l-ARG into the CVLM were abolished by prior microinjection of L-NAME in the CVLM of 2K1C and SHAM rats. Microinjection of L-NAME into the CVLM increased the sensitivity of reflex bradycardia in 2K1C animals. In contrast, the CVLM microinjection of L-ARG reduced reflex bradycardia only in SHAM rats. Vit C in the CVLM did not change reflex bradycardia in either 2K1C or in SHAM rats. These results suggest that increased oxidative stress in the CVLM during hypertension contributes to the reduced baroreflex sensitivity and to maintain hypertension in the 2K1C model. 相似文献
994.
Production of green chemicals and fuels using metabolically engineered organisms has been a promising alternative to petroleum-based production. Higher chain alcohols (C4-C8) are of interest because they can be used as chemical feedstock as well as fuels. Recently, the feasibility of n-hexanol synthesis using Escherichia coli has been demonstrated by extending the modified Clostridium CoA-dependent n-butanol synthesis pathway, thereby elongating carbon chain length via reactions in reversed β-oxidation, (or β-reduction). Here, we developed an anaerobic growth selection platform that allows selection or enrichment of enzymes for increased synthesis of C6 and C8 linear alcohols. Using this selection, we were able to improve the carbon flux towards the synthesis of C6 and C8 acyl-CoA intermediates. Replacement of the original enzyme Clostridium acetobutylicum Hbd with Ralstonia eutropha homologue PaaH1 increased production of n-hexanol by 10-fold. Further directed evolution by random mutagenesis of PaaH1 improved n-hexanol and n-octanol production. This anaerobic growth selection platform may be useful for selecting enzymes for production of long-chain alcohols and acids using this CoA-dependent pathway. 相似文献
995.
996.
L. Cohn Antonio F. Machado Robert Bier Marthe Cohn 《The Western journal of medicine》1988,149(3):303-306
To provide an effective continuum of the relief of severe carcinomatous pain with minimal side reactions, we initiated treatment with piroxicam (60 to 120 mg per day) and doxepin hydrochloride (25 to 225 mg per day). Of 30 patients presenting with severe pain of cancer of various origins, 7 continued to death with piroxicam and doxepin therapy. An additional 17 were successfully treated for 6 to 66 weeks with therapy reported here but, as disease progressed, required supplemental narcotics. The remaining six abandoned the use of piroxicam due to complications of therapy, which ranged from diarrhea to gastric perforation; serious complications were associated with patients'' failure to adhere to a prescribed regimen of sucralfate. Therapy with piroxicam and doxepin proved to be safe and efficacious. 相似文献
997.
da Silva Nayara Tayane Silva Lázara Aline Simões Reis Aryane Campos Machado Mariana de Matos Elyabe Monteiro Viccini Lyderson Facio Otoni Wagner Campos de Carvalho Ilio Fealho Rocha Diego Ismael da Silva Maurecilne Lemes 《Plant Cell, Tissue and Organ Culture》2020,142(3):613-624
Plant Cell, Tissue and Organ Culture (PCTOC) - Triploid plants represent an important resource for the breeding of fruit and ornamental plants. Here, we report a facile and robust system for... 相似文献
998.
Catarina Addobbati Jordão Cavalcanti Jaqueline de Azevêdo Silva Will de Barros Pita Tiago Degani Veit Odirlei Andre Monticielo Ricardo Machado Xavier João Carlos Tavares Brenol Cleiton Viegas Brenol Thiago Sotero Fragoso Alexandre Domingues Barbosa Ângela Luiza Branco Pinto Duarte Renê Donizeti Ribeiro Oliveira Paulo Louzada-Júnior Eduardo Antônio Donadi Sergio Crovella José Artur Bogo Chies Paula Sandrin-Garcia 《Molecular biology reports》2016,43(1):41-51
999.
1000.
M. A. Rajão D. G. Passos-Silva W. D. DaRocha G. R. Franco A. M. Macedo S. D. J. Pena S. M. Teixeira C. R. Machado 《Molecular microbiology》2009,71(1):185-197
DNA polymerase kappa (Polκ) is a low-fidelity polymerase that has the ability to bypass several types of lesions. The biological role of this enzyme, a member of the DinB subfamily of Y-family DNA polymerases, has remained elusive. In this report, we studied one of the two copies of Polκ from the protozoan Trypanosoma cruzi (TcPolκ). The role of this TcPolκ copy was investigated by analysing its subcellular localization, its activities in vitro , and performing experiments with parasites that overexpress this polymerase. The TcPOLK sequence has the N-terminal extension which is present only in eukaryotic DinB members, but its C-terminal region is more similar to prokaryotic and archaeal counterparts since it lacks C2 HC motifs and PCNA interaction domain. Our results indicate that in contrast to its previously described orthologues, this polymerase is localized to mitochondria. The overexpression of TcPOLK increases T. cruzi resistance to hydrogen peroxide, and in vitro polymerization assays revealed that TcPolκ efficiently bypasses 8-oxoguanine lesions. Remarkably, our results also demonstrate that the DinB subfamily of polymerases can participate in homologous recombination, based on our findings that TcPolκ increases T. cruzi resistance to high doses of gamma irradiation and zeocin and can catalyse DNA synthesis within recombination intermediates. 相似文献