全文获取类型
收费全文 | 490篇 |
免费 | 39篇 |
专业分类
529篇 |
出版年
2023年 | 6篇 |
2022年 | 4篇 |
2021年 | 10篇 |
2020年 | 6篇 |
2019年 | 15篇 |
2018年 | 13篇 |
2017年 | 12篇 |
2016年 | 19篇 |
2015年 | 31篇 |
2014年 | 42篇 |
2013年 | 35篇 |
2012年 | 41篇 |
2011年 | 32篇 |
2010年 | 26篇 |
2009年 | 19篇 |
2008年 | 26篇 |
2007年 | 38篇 |
2006年 | 25篇 |
2005年 | 20篇 |
2004年 | 31篇 |
2003年 | 26篇 |
2002年 | 25篇 |
2001年 | 2篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1998年 | 7篇 |
1997年 | 4篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 2篇 |
1991年 | 2篇 |
1987年 | 1篇 |
1984年 | 1篇 |
排序方式: 共有529条查询结果,搜索用时 15 毫秒
81.
Cristiana Pistol Tanase Simona Dima Mihaela Mihai Elena Raducan Mihnea Ioan Nicolescu Lucian Albulescu Bogdan Voiculescu Traian Dumitrascu Linda Maria Cruceru Mircea Leabu Irinel Popescu Mihail Eugen Hinescu 《Journal of molecular histology》2009,40(1):23-29
The assessment of caveolin-1 (Cav-1) as a marker of tumor aggressiveness in pancreatic ductal adenocarcinoma (PDAC). In this
study, we examined the expression of Cav-1 in 34 human PDAC tissue samples and the associated peritumoral tissues by immunohistochemistry
and western blot. Additionally, we correlated Cav-1 expression with other tissue (Ki-67, p53) and serum (CA 19-9) tumor markers.
In the tumor-derived tissue, both tumor cells and blood vessels expressed Cav-1. In contrast, in peritumoral tissue, Cav-1
expression was confined mainly to blood vessels and was only occasionally expressed in ductal or parenchymal cells. Western
blot analysis confirmed the overexpression of Cav-1 in pancreatic tumors compared with peritumoral tissue. Cav-1 expression
in tumor tissues was correlated with both the Ki-67 LI (r = 0.95, P < 0.0001) and p53 expression (χ2 = 9.91, P < 0.005). Overexpression of Cav-1 was associated with tumor size, grade and stage and Cav-1 expression in tumors was correlated
with an increased serum level of CA 19-9 (r = 0.795, P < 0.001). Based on the results of this study, the inclusion of Cav-1 in a putative panel of biomarkers predicting pancreatic
cancer aggressiveness is warranted. 相似文献
82.
Elena Perrin Marco Fondi Maria Cristiana Papaleo Isabel Maida Silvia Buroni Maria Rosalia Pasca Giovanna Riccardi Renato Fani 《BMC evolutionary biology》2010,10(1):164
Background
The genus Burkholderia includes a variety of species with opportunistic human pathogenic strains, whose increasing global resistance to antibiotics has become a public health problem. In this context a major role could be played by multidrug efflux pumps belonging to Resistance Nodulation Cell-Division (RND) family, which allow bacterial cells to extrude a wide range of different substrates, including antibiotics. This study aims to i) identify rnd genes in the 21 available completely sequenced Burkholderia genomes, ii) analyze their phylogenetic distribution, iii) define the putative function(s) that RND proteins perform within the Burkholderia genus and iv) try tracing the evolutionary history of some of these genes in Burkholderia. 相似文献83.
84.
ASPM and CITK regulate spindle orientation by affecting the dynamics of astral microtubules 下载免费PDF全文
85.
Omaira Vera Lizcano Sarah Stela Resende Yonne F Chehuan Marcus VG Lacerda Cristiana FA Brito Mariano G Zalis 《Memórias do Instituto Oswaldo Cruz》2014,109(7):948-951
The molecular basis of Plasmodium vivax chloroquine (CQ) resistance
is still unknown. Elucidating the molecular background of parasites that are
sensitive or resistant to CQ will help to identify and monitor the spread of
resistance. By genotyping a panel of molecular markers, we demonstrate a similar
genetic variability between in vitro CQ-resistant and sensitive phenotypes of
P. vivax parasites. However, our studies identified two
loci (MS8 and MSP1-B10) that could be used to discriminate
between both CQ-susceptible phenotypes among P. vivax isolates in
vitro. These preliminary data suggest that microsatellites may be used to identify
and to monitor the spread of P. vivax-resistance around the
world. 相似文献
86.
Daniela Camargos Costa Ana Paula Madureira Lara Cotta Amaral Bruno Ant?nio Marinho Sanchez Luciano Teixeira Gomes Cor Jésus Fernandes Fontes Jean Ezequiel Limongi Cristiana Ferreira Alves de Brito Luzia Helena Carvalho 《Memórias do Instituto Oswaldo Cruz》2014,109(1):21-28
The polymerase chain reaction (PCR)-based methods for the diagnosis of malaria
infection are expected to accurately identify submicroscopic parasite carriers.
Although a significant number of PCR protocols have been described, few studies have
addressed the performance of PCR amplification in cases of field samples with
submicroscopic malaria infection. Here, the reproducibility of two well-established
PCR protocols (nested-PCR and real-time PCR for the Plasmodium 18
small subunit rRNA gene) were evaluated in a panel of 34 blood field samples from
individuals that are potential reservoirs of malaria infection, but were negative for
malaria by optical microscopy. Regardless of the PCR protocol, a large variation
between the PCR replicates was observed, leading to alternating positive and negative
results in 38% (13 out of 34) of the samples. These findings were quite different
from those obtained from the microscopy-positive patients or the unexposed
individuals; the diagnosis of these individuals could be confirmed based on the high
reproducibility and specificity of the PCR-based protocols. The limitation of PCR
amplification was restricted to the field samples with very low levels of
parasitaemia because titrations of the DNA templates were able to detect < 3
parasites/µL in the blood. In conclusion, conventional PCR protocols require careful
interpretation in cases of submicroscopic malaria infection, as inconsistent and
false-negative results can occur. 相似文献
87.
Cruz M Freitas F Torres CA Reis MA Alves VD 《International journal of biological macromolecules》2011,48(4):695-699
The effect of temperature on the rheology of a new fucose-containing extracellular polysaccharide (EPS) was evaluated. The steady state data revealed a shear-thinning behavior, with the viscosity being immediately recovered when the shear rate was decreased. The mechanical spectra indicated viscous solutions with entangled polymer molecules in the range of temperatures studied (from 15 °C to 65 °C). In addition, the Time-Temperature Superposition principle was successfully applied and the Cox-Merz rule was valid, reinforcing the idea of a thermorheologically simple behavior for the EPS in aqueous solution. Furthermore, the viscous and viscoelastic properties at 25 °C were maintained after consecutive heating and cooling cycles, indicating a good thermal stability under temperature fluctuations. 相似文献
88.
Di Giuro CM Buongiorno D Leitner E Straganz GD 《Journal of inorganic biochemistry》2011,105(9):1204-1211
Mononuclear nonheme iron enzymes (MNHEs) catalyze a range of very diverse reactions in O2 metabolism, but they share a common principle active-site organization. To investigate a putative catalytic promiscuity of these enzymatic metal centers, we studied the reactivity of the 3-His ligated metal center of diketone cleaving enzyme (Dke1) toward non-native substrates, with a focus on alternative O2 dependent reactions. From a screening approach, which aims at eliminating steric factors by including minimal substrate-substructures, three alternative, ‘non-β-dicarbonyl-cleavage’ reactions are identified, among them an unprecedented oxygenation of maltol. Maltol cleavage is characterized by steady state and fast kinetic measurements and shows an O2 concentration dependent rate determining step kcat/KM(O2) of 0.3 mM− 1 s− 1 and a strict coupling of O2 reduction and substrate oxidation. Furthermore, the catalytic potential of the 3-His metal center for O2 dependent catechol ring-cleavage and phenylpyruvate oxidation (PP) is demonstrated. 相似文献
89.
Edelmann B Bertsch U Tchikov V Winoto-Morbach S Perrotta C Jakob M Adam-Klages S Kabelitz D Schütze S 《The EMBO journal》2011,30(2):379-394
We previously demonstrated that tumour necrosis factor (TNF)-induced ceramide production by endosomal acid sphingomyelinase (A-SMase) couples to apoptosis signalling via activation of cathepsin D and cleavage of Bid, resulting in caspase-9 and caspase-3 activation. The mechanism of TNF-mediated A-SMase activation within the endolysosomal compartment is poorly defined. Here, we show that TNF-induced A-SMase activation depends on functional caspase-8 and caspase-7 expression. The active forms of all three enzymes, caspase-8, caspase-7 and A-SMase, but not caspase-3, colocalize in internalized TNF receptosomes. While caspase-8 and caspase-3 are unable to induce activation of purified pro-A-SMase, we found that caspase-7 mediates A-SMase activation by direct interaction resulting in proteolytic cleavage of the 72-kDa pro-A-SMase zymogen at the non-canonical cleavage site after aspartate 253, generating an active 57 kDa A-SMase molecule. Caspase-7 down modulation revealed the functional link between caspase-7 and A-SMase, confirming proteolytic cleavage as one further mode of A-SMase activation. Our data suggest a signalling cascade within TNF receptosomes involving sequential activation of caspase-8 and caspase-7 for induction of A-SMase activation by proteolytic cleavage of pro-A-SMase. 相似文献
90.
Fathalli A Jenhani AB Moreira C Welker M Romdhane M Antunes A Vasconcelos V 《Systematic and applied microbiology》2011,34(4):303-310
This study presents a genetic characterization of 27 potentially toxic cyanobacterial strains isolated from seven reservoirs located in the north and centre of Tunisia. These strains belonged mainly to Microcystis aeruginosa, Cylindrospermopsis raciborskii and Planktothrix agardhii species. Their toxicological potential was evaluated by molecular biology tools, which showed that none of the isolated strains carried segments of the gene cluster responsible for the production of cylindrospermopsin and saxitoxin. The majority of Microcystis isolates were able to synthesize microcystin, since they presented the six characteristic segments of the microcystin synthetase mcy cluster (mcyA, -B, -C, -D, -E and -G). This was further confirmed by MALDI-TOF analysis that showed the presence of eight microcystin variants, including microcystin-LR. The taxonomic identification of the strains was assessed based on the variability of the 16S rRNA gene sequences. Furthermore, the 16S-23S rRNA ITS sequences of Microcystis isolates and rpoC1 sequences of Cylindrospermopsis strains were also used in the phylogenetic analysis. 相似文献