全文获取类型
收费全文 | 1623篇 |
免费 | 98篇 |
出版年
2023年 | 16篇 |
2022年 | 21篇 |
2021年 | 79篇 |
2020年 | 50篇 |
2019年 | 82篇 |
2018年 | 71篇 |
2017年 | 59篇 |
2016年 | 76篇 |
2015年 | 116篇 |
2014年 | 112篇 |
2013年 | 144篇 |
2012年 | 148篇 |
2011年 | 155篇 |
2010年 | 101篇 |
2009年 | 65篇 |
2008年 | 65篇 |
2007年 | 53篇 |
2006年 | 56篇 |
2005年 | 51篇 |
2004年 | 43篇 |
2003年 | 36篇 |
2002年 | 22篇 |
2001年 | 14篇 |
2000年 | 10篇 |
1999年 | 2篇 |
1998年 | 5篇 |
1997年 | 4篇 |
1996年 | 5篇 |
1995年 | 6篇 |
1994年 | 5篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1990年 | 7篇 |
1988年 | 2篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1982年 | 2篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1972年 | 4篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1969年 | 1篇 |
1967年 | 3篇 |
1966年 | 2篇 |
1965年 | 2篇 |
排序方式: 共有1721条查询结果,搜索用时 15 毫秒
1.
Raimundo Wagner Souza Aguiar Suetonio Fernandes dos Santos Fabricio da Silva Morgado Sergio Donizeti Ascencio Magnólia de Mendon?a Lopes Kelvinson Fernandes Viana Julcemar Didonet Bergmann Morais Ribeiro 《PloS one》2015,10(2)
This study investigated the toxic effects of essential oils isolated from Siparuna guianensis against Aedes aegypti, Culex quinquefasciatus (eggs, larvae, pupae, and adult) and Aedes albopictus (C6/36) cells. The oviposition-deterring activity, egg viability, and repellence activity in the presence of different essential oils concentrations were determined. The essential oils showed high toxicity to all developmental stages of A. aegypti and C. quinquefasciatus. Furthermore, the oils also showed high repellent activity towards the adult stage of mosquitoes (0.025 to 0.550 μg/cm2 skin conferred 100% repellence up to 120 min) and in contact with cultured insect cells (C6/36) induced death possibly by necrosis. The results presented in this work show the potential of S. guianensis essential oils for the development of an alternative and effective method for the natural control of mosquitoes in homes and urban areas. 相似文献
2.
Graziele Fonseca de Sousa Maira de Assis Lima Débora Fernandes Custodio Vanessa Morais Freitas Gisele Monteiro 《PloS one》2015,10(12)
The use of carboplatin in cancer chemotherapy is limited by the emergence of drug resistance. To understand the molecular basis for this resistance, a chemogenomic screen was performed in 53 yeast mutants that had previously presented strong sensitivity to this widely used anticancer agent. Thirty-four mutants were responsive to carboplatin, and from these, 21 genes were selected for further studies because they have human homologues. Sixty percent of these yeast genes possessed human homologues which encoded proteins that interact with cullin scaffolds of ubiquitin ligases, or whose mRNA are under the regulation of Human antigen R (HuR) protein. Both HuR and cullin proteins are regulated through NEDDylation post-translational modification, and so our results indicate that inhibition of this process should sensitise resistant tumour cells to carboplatin. We showed that treatment of a tumour cell line with MLN4924, a NEDDylation inhibitor, overcame the resistance to carboplatin. Our data suggest that inhibition of NEDDylation may be a useful strategy to resensitise tumour cells in patients that have acquired carboplatin resistance. 相似文献
3.
Rubina L. Caldeira Tiago M. Martins Carlos Novo Virgílio do Rosário 《Experimental parasitology》2009,122(2):97-7642
Plasmodium cysteine proteases have been shown to be immunogenic and are being used as malaria potential serodiagnostic markers and vaccine targets. Genes encoding two Plasmodium chabaudi cysteine proteases chabaupain-1 (CP-1) and chabaupain-2 (CP-2) were identified and further expressed in Escherichia coli. Solubilisation of recombinant CP-1 and CP-2 was achieved by decreasing the temperature of induction.Anopheles gambiae tissues infected with Plasmodium were analyzed by Western blotting using the anti-CP-1 antibody showing that CP-1 is only present in the A. gambiae midguts being absent from other infected mosquito biological material. Anti-CP-1 anti-serum recognized a 30 kDa band in P. chabaudi, Plasmodium berghei and Plasmodium yoelii lysates but does not recognize the recombinant CP-2 extracts suggesting high antibody specificity. 相似文献
4.
5.
6.
Carolina G. dos Santos André L. Silva Flavio L. Souza Alexandre J. C. Lanfredi Paolo Di Mascio Otaciro R. Nascimento Tiago Rodrigues Iseli L. Nantes 《PloS one》2013,8(10)
The present study shows the factors that modulate the photodamage promoted by phenothiazines. Cytochrome c was irradiated with UV light for 120 min, over a pH range from 4.0 to 8.0, in the absence and in the presence of different concentrations of thioridazine (TR) and fluphenazine (FP). In the absence of phenothiazines, the maximal rate of a Soret band blue shift (nm/min) from 409 to 406 nm was obtained at pH 4.0 (0.028 nm/min). The presence of phenothiazines at the concentration range 10-25 µmol/L amplified and accelerated a cytochrome c blue shift (409 to 405 nm, at a rate = 0.041 nm/min). Above 25 µmol/L, crescent concentrations of phenothiazines contributed to cytochrome c protection with (maximal at 2500 µmol/L). Scanning electronic microscopy revealed the formation of nanostructures. The pH also influenced the effect of low phenothiazine concentrations on cytochrome c. Thus, the predominance of phenothiazine-promoted cytochrome c damage or protection depends on a balance of the following factors: the yield of photo-generated drug cation radicals, which is favored by acidic pH; the stability of the cation radicals, which is favored by the drug aggregation; and the cytochrome c structure, modulated by the pH. 相似文献
7.
Danielle B. Morais Mirlaine S. Barros Tarcízio A. R. Paula Mariella B. D. Freitas Marcos L. M. Gomes Sérgio L. P. Matta 《PloS one》2014,9(7)
Due to the scarcity of information about patterns of spermatogenesis in bats, this study aimed to provide information on the testicular activity of the bat Sturnira lilium along the annual seasons. Thus, a series of morphometrical and stereological analyses were made using the testes of adult S. lilium in order to achieve a better understanding of the sperm production dynamics. Light and transmission electron microscopy analyses were performed in testicular fragments of animals captured during dry and rainy seasons. The testes followed the pattern of organization described for other mammals, and there were no morphological differences between organs collected either in dry or in rainy seasons. Each tubular cross-section in stage 1 was made of 0.5 type-A spermatogonia, 4.4 primary spermatocytes in preleptotene/leptotene, 3.7 in zygotene, 11.9 in pachytene, 35.6 round spermatids and 8.5 Sertoli cells. The mitotic and meiotic indexes were 15.4 and 2.9 cells, respectively, while the spermatogenesis yield was 68.7 cells. The testicular sperm reserves was 37.61×106 cells, and daily sperm production per gram of testis averaged 209.68×106 cells, both highest averages occurring in the rainy season. S. lilium male bats have a continuous reproductive pattern, high spermatogenesis yield and low support capacity by the Sertoli cells. 相似文献
8.
Laura Roesler Nery Natalia Silva Eltz Cristiana Hackman Raphaela Fonseca Stefani Altenhofen Heydi Noriega Guerra Vanessa Morais Freitas Carla Denise Bonan Monica Ryff Moreira Roca Vianna 《PloS one》2014,9(9)
Alzheimer’s disease (AD) is a devastating neurodegenerative disorder with no effective treatment and commonly diagnosed only on late stages. Amyloid-β (Aβ) accumulation and exacerbated tau phosphorylation are molecular hallmarks of AD implicated in cognitive deficits and synaptic and neuronal loss. The Aβ and tau connection is beginning to be elucidated and attributed to interaction with different components of common signaling pathways. Recent evidences suggest that non-fibrillary Aβ forms bind to membrane receptors and modulate GSK-3β activity, which in turn phosphorylates the microtubule-associated tau protein leading to axonal disruption and toxic accumulation. Available AD animal models, ranging from rodent to invertebrates, significantly contributed to our current knowledge, but complementary platforms for mechanistic and candidate drug screenings remain critical for the identification of early stage biomarkers and potential disease-modifying therapies. Here we show that Aβ1–42 injection in the hindbrain ventricle of 24 hpf zebrafish embryos results in specific cognitive deficits and increased tau phosphorylation in GSK-3β target residues at 5dpf larvae. These effects are reversed by lithium incubation and not accompanied by apoptotic markers. We believe this may represent a straightforward platform useful to identification of cellular and molecular mechanisms of early stage AD-like symptoms and the effects of neuroactive molecules in pharmacological screenings. 相似文献
9.
10.
We studied the latent factor structure of the Beck Depression Inventory (BDI) under the light of Multidimensional Item Response Theory models. Under a Bayesian Markov chain Monte Carlo setting, we chose the most adequate model, estimated its parameters and verified its fit to the data. An evaluation of the inventory in terms of the assumed dimensions seems to agree with previous investigations in the factor structure of the BDI present in the literature. Cognitive and somatic‐affective latent traits were identified in the analysis making possible the interpretation of symptom evolution along these dimensions, in terms of probability of their appearance. 相似文献