全文获取类型
收费全文 | 4137篇 |
免费 | 266篇 |
出版年
2024年 | 4篇 |
2023年 | 37篇 |
2022年 | 69篇 |
2021年 | 114篇 |
2020年 | 115篇 |
2019年 | 135篇 |
2018年 | 146篇 |
2017年 | 125篇 |
2016年 | 217篇 |
2015年 | 269篇 |
2014年 | 303篇 |
2013年 | 360篇 |
2012年 | 355篇 |
2011年 | 319篇 |
2010年 | 225篇 |
2009年 | 182篇 |
2008年 | 226篇 |
2007年 | 202篇 |
2006年 | 179篇 |
2005年 | 158篇 |
2004年 | 147篇 |
2003年 | 104篇 |
2002年 | 118篇 |
2001年 | 37篇 |
2000年 | 30篇 |
1999年 | 37篇 |
1998年 | 19篇 |
1997年 | 11篇 |
1996年 | 10篇 |
1995年 | 10篇 |
1994年 | 9篇 |
1993年 | 9篇 |
1992年 | 10篇 |
1991年 | 10篇 |
1990年 | 10篇 |
1989年 | 8篇 |
1988年 | 11篇 |
1986年 | 7篇 |
1984年 | 3篇 |
1983年 | 7篇 |
1982年 | 5篇 |
1981年 | 4篇 |
1980年 | 5篇 |
1979年 | 6篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1975年 | 4篇 |
1973年 | 3篇 |
1972年 | 5篇 |
1966年 | 3篇 |
排序方式: 共有4403条查询结果,搜索用时 15 毫秒
991.
Complete genome sequencing of a novel newcastle disease virus isolate circulating in layer chickens in the dominican republic 总被引:1,自引:0,他引:1
SC Courtney D Gomez L Susta N Hines JC Pedersen PJ Miller CL Afonso 《Journal of virology》2012,86(17):9550
Newcastle disease virus (NDV) was isolated from an outbreak in layer chickens in the Dominican Republic in 2008. Infections with this isolate led to a 100% apparent case fatality rate in birds. Complete genome sequencing revealed that the isolate does not belong to any of the previously described NDV genotypes. Similarly, large differences were observed in the amino acid sequence of the fusion and hemagglutinin-neuraminidase proteins in comparison with all known NDV genotypes, suggesting the existence of an unknown reservoir for NDV. The work presented here represents the first complete genome sequence of NDV in the Dominican Republic. 相似文献
992.
Lysine degradation through the saccharopine pathway has been shown only in plants and animals. Here, we show that bacteria possess the genes encoding lysine-ketoglutarate reductase (LKR) and saccharopine dehydrogenase (SDH). In Silicibacter, the contiguous lkr and sdh genes are interspersed, in another frame, by a polypeptide of unknown function. The bacterial enzyme does not contain the 110-amino-acid interdomain (ID) that intersperses the LKR and SDH domains of the plant enzyme. The ID was found in Cyanobacteria interspersing polypeptides without similarities and activities of LKR and SDH. The LKR/SDH bifunctional polypeptide of animals and plants may have arisen from a α-proteobacterium with a configuration similar to that of Silicibacter, whereas the ID in the plant enzyme may have been inherited from Cyanobacteria. 相似文献
993.
In this study the interaction of the antitumoral drug daunorubicin with egg phosphatidylcholine (EPC) liposomes, used as a
cell membrane model, was quantified by determination of the partition coefficient (K
p). The liposome/aqueous-phase K
p of daunorubicin was determined by derivative spectrophotometry and measurement of the zeta-potential. Mathematical models
were used to fit the experimental data, enabling determination of K
p. In the partition of daunorubicin within the membrane both superficial electrostatic and inner hydrophobic interactions seem
to be involved. The results are affected by the two types of interaction since spectrophotometry measures mainly hydrophobic
interactions, while zeta-potential is affected by both interpenetration of amphiphilic charged molecules in the bilayer and
superficial electrostatic interaction. Moreover, the degree of the partition of daunorubicin with the membrane changes with
the drug concentration, due mainly to saturation factors. Derivative spectrophotometry and zeta-potential variation results,
together with the broad range of concentrations studied, revealed the different types of interactions involved. The mathematical
formalism applied also allowed quantification of the number of lipid molecules associated with one drug molecule. 相似文献
994.
Coutinho LB Gomes AO Araújo EC Barenco PV Santos JL Caixeta DR Silva DA Cunha-Júnior JP Ferro EA Silva NM 《International journal for parasitology》2012,42(4):341-352
Congenital toxoplasmosis is associated with adverse pregnancy outcome. Despite the type 1 immune response, C57BL/6 mice are more susceptible than BALB/c mice to Toxoplasma gondii infection. Additionally, successful pregnancy appears to be correlated with type 2 T helper maternal immunity and regulatory T cells. In order to investigate the mechanisms of susceptibility/resistance to congenital toxoplasmosis in mice with different genetic backgrounds and the influence of inducible nitric oxide synthase in pregnancy outcome, groups of C57BL/6, BALB/c and C57BL/6 iNOS(-/-) females were orally infected with T. gondii ME-49 strain on day 1 of pregnancy and were sacrificed on day 8 p.i. and day 19 p.i. The uterus and placenta were evaluated for the foetal resorption rate, parasite load, immunological and histological changes. C57BL/6 mice presented inflammatory foci in the decidua (endometrium) of the uterus at a higher frequency than BALB/c mice on day 8 p.i., and a large number of pregnant C57BL/6 mice presented necrotic implantation sites. The parasite was seldom found in the uterus or placenta of either lineage of mice. Interestingly, there was no observed difference in inducible nitric oxide synthase expression in the uterus and placenta of infected mice. In addition, higher levels of TNF-α were detected in serum samples from C57BL/6 mice compared with BALB/c mice. Accordingly, C57BL/6 mice presented with levels of 90% abortion compared with 50% in BALB/c mice on day 19 p.i. C57BL/6 iNOS(-/-) mice showed low placental parasite counts and high absorption rates, similar to wild type mice. The data suggest that the impaired pregnancy outcome due to T. gondii infection in C57BL/6 mice could be associated with a higher inflammatory response leading to cell apoptosis and necrosis of implantation sites compared with BALB/c mice, and this phenomenon was not due to inducible nitric oxide synthase expression in the decidua. 相似文献
995.
de Sá Morais LL Garza DR Loureiro EC Nunes KN Vellasco RS da Silva CP Nunes MR Thompson CC Vicente AC Santos EC 《Journal of bacteriology》2012,194(10):2772
We report the genome sequence of Vibrio cholerae strain IEC224, which fails to ferment sucrose. It was isolated from a cholera outbreak in the Amazon. The defective sucrose phenotype was determined to be due to a frameshift mutation, and a molecular marker of the Latin American main epidemic lineage was identified. 相似文献
996.
997.
Amato AA Rajagopalan S Lin JZ Carvalho BM Figueira AC Lu J Ayers SD Mottin M Silveira RL Souza PC Mourão RH Saad MJ Togashi M Simeoni LA Abdalla DS Skaf MS Polikparpov I Lima MC Galdino SL Brennan RG Baxter JD Pitta IR Webb P Phillips KJ Neves FA 《The Journal of biological chemistry》2012,287(33):28169-28179
The recent discovery that peroxisome proliferator-activated receptor γ (PPARγ) targeted anti-diabetic drugs function by inhibiting Cdk5-mediated phosphorylation of the receptor has provided a new viewpoint to evaluate and perhaps develop improved insulin-sensitizing agents. Herein we report the development of a novel thiazolidinedione that retains similar anti-diabetic efficacy as rosiglitazone in mice yet does not elicit weight gain or edema, common side effects associated with full PPARγ activation. Further characterization of this compound shows GQ-16 to be an effective inhibitor of Cdk5-mediated phosphorylation of PPARγ. The structure of GQ-16 bound to PPARγ demonstrates that the compound utilizes a binding mode distinct from other reported PPARγ ligands, although it does share some structural features with other partial agonists, such as MRL-24 and PA-082, that have similarly been reported to dissociate insulin sensitization from weight gain. Hydrogen/deuterium exchange studies reveal that GQ-16 strongly stabilizes the β-sheet region of the receptor, presumably explaining the compound's efficacy in inhibiting Cdk5-mediated phosphorylation of Ser-273. Molecular dynamics simulations suggest that the partial agonist activity of GQ-16 results from the compound's weak ability to stabilize helix 12 in its active conformation. Our results suggest that the emerging model, whereby "ideal" PPARγ-based therapeutics stabilize the β-sheet/Ser-273 region and inhibit Cdk5-mediated phosphorylation while minimally invoking adipogenesis and classical agonism, is indeed a valid framework to develop improved PPARγ modulators that retain antidiabetic actions while minimizing untoward effects. 相似文献
998.
Genetically modified sugarcane for bioenergy generation 总被引:2,自引:0,他引:2
Arruda P 《Current opinion in biotechnology》2012,23(3):315-322
Sugarcane breeding has significantly progressed over the past 30 years, but attempts to further increase crop yield have been limited due to the complexity of the sugarcane genome. An alternative to boost the crop yield is the introduction of genes encoding desirable traits in the elite sugarcane cultivars. Genetically modified sugarcane with increased yield and pest and disease resistance has already proven its value not only by the increased sugar content but also for the improvement of the crop performance. However, transgene stability is still a challenge since transgene silencing seems to occur in a large proportion of genetically modified sugarcane plants. In addition, regulatory issues associated with the crop propagation model will also be a challenge to the commercial approval of genetically modified sugarcane. 相似文献
999.
Wellington Adriano Moreira Peres Luiz Antonio Carlos Bertollo Paulo Andreas Buckup Daniel Rodrigues Blanco Daniel Luis Zanella Kantek Orlando Moreira-Filho 《Reviews in Fish Biology and Fisheries》2012,22(2):519-526
The Astyanax species of the bimaculatus group include morphologically similar representatives that share the same color pattern, corresponding to at least 20 species.
Specimens from the S?o Francisco River basin and from the Grande River (Upper Paraná basin) are included in this group. In
the early 1960’s, the Piumhi River, an original tributary of the Grande River, was transposed to the S?o Francisco River basin
due to the construction of the Furnas Hydroelectric Power, in the state of Minas Gerais, Brazil. In this context, we characterized
representatives of the bimaculatus group from both basins and from the transposition region of the Piumhi River, using chromosome characteristics obtained by
conventional analyzes and fluorescence in situ hybridization with rDNA probes. All the analyzed specimens presented 2n = 50
chromosomes and similar localization of the nucleolus organizer regions (Ag-NORs), 18S rDNA and 5S rDNA sites. However, diagnostic
chromosome differences were detected concerning the number of submetacentric and acrocentric chromosomes in the karyotypes,
making possible the characterization of five distinct karyotypes (Cytotypes A–E), where the specimens from the S?o Francisco
and from the Grande River correspond to Cytotypes A and B, respectively. In addition, these two Cytotypes were sympatrically
found in the Piumhi River with specimens carrying a clear intermediate karyotype (Cytotype C), as well as with others harboring
different karyotypes (Cytotypes D and E). Our data indicate that Cytotypes A and B probably diverged from each other during
the prior geographic isolation. However, despite their chromosomal differentiations, they still maintain a close relationship
which allows interbreeding and the formation of a secondary hybrid zone, due to the breakdown of the geographic isolation. 相似文献
1000.
Janice de Almeida Engler Tina Kyndt Paulo Vieira Elke Van Cappelle Veronique Boudolf Vanesa Sanchez Carolina Escobar Lieven De Veylder Gilbert Engler Pierre Abad Godelieve Gheysen 《The Plant journal : for cell and molecular biology》2012,72(2):185-198
The establishment of galls and syncytia as feeding sites induced by root‐knot and cyst nematodes, respectively, involves a progressive increase in nuclear and cellular size. Here we describe the functional characterization of endocycle activators CCS52A, CCS52B and a repressor of the endocycle, DEL1, during two types of nematode feeding site development in Arabidopsis thaliana. In situ hybridization analysis showed that expression of CCS52A1 and CCS52B was strongly induced in galls and syncytia and DEL1 was stably but weakly expressed throughout feeding site development. Down‐regulation and over‐expression of CCS52 and DEL1 in Arabidopsis drastically affected giant cell and syncytium growth, resulting in restrained nematode development, illustrating the need for mitotic activity and endo‐reduplication for feeding site maturation. Exploiting the mechanism of endo‐reduplication may be envisaged as a strategy to control plant‐parasitic nematodes. 相似文献