全文获取类型
收费全文 | 1706篇 |
免费 | 81篇 |
专业分类
1787篇 |
出版年
2024年 | 2篇 |
2023年 | 21篇 |
2022年 | 31篇 |
2021年 | 63篇 |
2020年 | 43篇 |
2019年 | 48篇 |
2018年 | 57篇 |
2017年 | 60篇 |
2016年 | 90篇 |
2015年 | 102篇 |
2014年 | 119篇 |
2013年 | 129篇 |
2012年 | 146篇 |
2011年 | 118篇 |
2010年 | 98篇 |
2009年 | 67篇 |
2008年 | 93篇 |
2007年 | 89篇 |
2006年 | 57篇 |
2005年 | 46篇 |
2004年 | 54篇 |
2003年 | 47篇 |
2002年 | 37篇 |
2001年 | 20篇 |
2000年 | 20篇 |
1999年 | 20篇 |
1998年 | 14篇 |
1997年 | 9篇 |
1996年 | 7篇 |
1995年 | 6篇 |
1994年 | 2篇 |
1993年 | 4篇 |
1992年 | 7篇 |
1991年 | 5篇 |
1989年 | 5篇 |
1988年 | 4篇 |
1987年 | 4篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1984年 | 6篇 |
1983年 | 4篇 |
1981年 | 4篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1975年 | 2篇 |
1974年 | 3篇 |
1973年 | 2篇 |
1967年 | 3篇 |
1963年 | 1篇 |
1958年 | 1篇 |
排序方式: 共有1787条查询结果,搜索用时 15 毫秒
11.
Marcelo U. Ferreira Isabel Giacomini Priscila M. Sato Barbara H. Loureno Vanessa C. Nicolete Lewis F. Buss Alicia Matijasevich Marcia C. Castro Marly A. Cardoso for the MINA-Brazil Working Group 《PLoS neglected tropical diseases》2022,16(7)
BackgroundThe epidemiology of childhood SARS-CoV-2 infection and COVID-19-related illness remains little studied in high-transmission tropical settings, partly due to the less severe clinical manifestations typically developed by children and the limited availability of diagnostic tests. To address this knowledge gap, we investigate the prevalence and predictors of SARS-CoV-2 infection (either symptomatic or not) and disease in 5 years-old Amazonian children.Methodology/Principal findingsWe retrospectively estimated SARS-CoV-2 attack rates and the proportion of infections leading to COVID-19-related illness among 660 participants in a population-based birth cohort study in the Juruá Valley, Amazonian Brazil. Children were physically examined, tested for SARS-CoV-2 IgG and IgM antibodies, and had a comprehensive health questionnaire administered during a follow-up visit at the age of 5 years carried out in January or June-July 2021. We found serological evidence of past SARS-CoV-2 infection in 297 (45.0%; 95% confidence interval [CI], 41.2–48.9%) of 660 cohort participants, but only 15 (5.1%; 95% CI, 2.9–8.2%) seropositive children had a prior medical diagnosis of COVID-19 reported by their mothers or guardians. The period prevalence of clinically apparent COVID-19, defined as the presence of specific antibodies plus one or more clinical symptoms suggestive of COVID-19 (cough, shortness of breath, and loss of taste or smell) reported by their mothers or guardians since the pandemic onset, was estimated at 7.3% (95% CI, 5.4–9.5%). Importantly, children from the poorest households and those with less educated mothers were significantly more likely to be seropositive, after controlling for potential confounders by mixed-effects multiple Poisson regression analysis. Likewise, the period prevalence of COVID-19 was 1.8-fold (95%, CI 1.2–2.6-fold) higher among cohort participants exposed to food insecurity and 3.0-fold (95% CI, 2.8–3.5-fold) higher among those born to non-White mothers. Finally, children exposed to household and family contacts who had COVID-19 were at an increased risk of being SARS-CoV-2 seropositive and–even more markedly–of having had clinically apparent COVID-19 by the age of 5 years.Conclusions/SignificanceChildhood SARS-CoV-2 infection and COVID-19-associated illness are substantially underdiagnosed and underreported in the Amazon. Children in the most socioeconomically vulnerable households are disproportionately affected by SARS-CoV-2 infection and disease. 相似文献
12.
Isabel C.M. Fensterseifer Mário R. Felício Eliane S.F. Alves Marlon H. Cardoso Marcelo D.T. Torres Carolina O. Matos Osmar N. Silva Timothy K. Lu Maurício V. Freire Natan C. Neves Sónia Gonçalves Luciano M. Lião Nuno C. Santos William F. Porto Cesar de la Fuente-Nunez Octavio L. Franco 《生物化学与生物物理学报:生物膜》2019,1861(7):1375-1387
Infections caused by Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa foremost among them, constitute a major worldwide health problem. Bioinformatics methodologies are being used to rationally design new antimicrobial peptides, a potential alternative for treating these infections. One of the algorithms used to develop antimicrobial peptides is the Joker, which was used to design the peptide PaDBS1R6. This study evaluates the antibacterial activities of PaDBS1R6 in vitro and in vivo, characterizes the peptide interaction to target membranes, and investigates the PaDBS1R6 structure in contact with mimetic vesicles. Moreover, we demonstrate that PaDBS1R6 exhibits selective antimicrobial activity against Gram-negative bacteria. In the presence of negatively charged and zwitterionic lipids the structural arrangement of PaDBS1R6 transits from random coil to α-helix, as characterized by circular dichroism. The tertiary structure of PaDBS1R6 was determined by NMR in zwitterionic dodecylphosphocholine (DPC) micelles. In conclusion, PaDBS1R6 is a candidate for the treatment of nosocomial infections caused by Gram-negative bacteria, as template for producing other antimicrobial agents. 相似文献
13.
14.
Ricardo Cardoso Neves Reinhardt Møbjerg Kristensen 《Organisms Diversity & Evolution》2014,14(2):163-171
Loricifera is a phylum of minute animals that live exclusively in marine sediments. A total of 33 species have been described so far in this phylum; however, several more are already known from preliminary observations. Loriciferans are characterised by a complex life cycle, which involves a succession of several adult and larval stages. Here, we describe a new type of loriciferan larval stage: the Shira larva. The gross morphology of this larva is generally similar to that of the most prominent larval type of Loricifera, the so-called Higgins larva. However, the Shira larva possesses a number of unique features, namely (1) a single pair of anteroventral setae is present in the most anterior region of the abdomen, (2) the bases of the anteroventral setae are very large and swollen, (3) the thorax and abdomen are thinner than the introvert and (4) the abdominal region is divided into five sub-regions. Accordingly, we described the new species, Tenuiloricus shirayamai gen. nov. et sp. nov. (incertae sedis). The new findings are discussed from a comparative perspective with the Higgins larva as well as with the fossil of a putative loriciferan larval stage from the Middle Cambrian. 相似文献
15.
Recent discovery of 5-hydroxymethylcytosine (5hmC) in genomic DNA raises the question how this sixth base is recognized by cellular proteins. In contrast to the methyl-CpG binding domain (MBD) of MeCP2, we found that the SRA domain of Uhrf1, an essential factor in DNA maintenance methylation, binds 5hmC and 5-methylcytosine containing substrates with similar affinity. Based on the co-crystal structure, we performed molecular dynamics simulations of the SRA:DNA complex with the flipped cytosine base carrying either of these epigenetic modifications. Our data indicate that the SRA binding pocket can accommodate 5hmC and stabilizes the flipped base by hydrogen bond formation with the hydroxyl group. 相似文献
16.
Amphiphilic detergent-soluble acetylcholinesterase (AChE) from Torpedo is converted to a hydrophilic form by digestion with phospholipase C from Trypanosoma brucei or from Bacillus cereus. This lipase digestion uncovers an immunological determinant which crossreacts with a complex carbohydrate structure present in the hydrophilic form of all variant surface glycoproteins (VSG) of T. brucei. This crossreacting determinant is also detected in human erythrocyte AChE after digestion with T. brucei lipase. From these results we conclude that the glycophospholipid anchors of protozoan VSG and of AChE of the two vertebrates share common structural features, suggesting that this novel type of membrane anchor has been conserved during evolution. 相似文献
17.
18.
In this paper, we further investigate the new paradigm for the rupture of thin cap fibroatheroma (TCFA) proposed in Vengrenyuk et al. (2006 PNAS 103:14678) using a multilevel micro-CT based 3D numerical modeling. The new paradigm proposes that the rupture of TCFA is due to stress-induced interfacial debonding of cellular--level, 10-20 microm microcalcifications in the fibrous cap proper. Such microcalcifications, which lie below the visibility of current in vivo imaging techniques, were detected for the first time using confocal microscopy and high resolution microcomputed tomography (micro-CT) imaging in Vengrenyuk et al. (2006) In the present study, we use high resolution (7 microm) micro-CT imaging to construct accurate geometries of both these microcalcifications and larger mm size macrocalcifications at the cap shoulders to evaluate their biomechanical stability. The analysis shows that cellular-level calcifications by themselves are not dangerous unless they lie in a region of high background stress. This high level of background stress only occurs in caps whose thickness is < approximately 80 microm. Whereas a spherical microcalcification will increase peak circumferential stress (PCS) by a factor of two, in agreement with previous local analytical solutions, this can be increased several fold by elongated microcalcifications. The most dangerous situation is when a microinclusion appears in close proximity to a region where the PCS is already high. This stress will be substantially increased if the inclusion is elongated. In contrast, macrocalcifications at the cap shoulders are shown to actually increase plaque stability. 相似文献
19.
Romeu Cardoso Guimarães 《Origins of life and evolution of the biosphere》2011,41(4):357-371
An investigation of the biosynthesis pathways producing glycine and serine was necessary to clarify an apparent inconsistency
between the self-referential model (SRM) for the formation of the genetic code and the model of coevolution of encodings and
of amino acid biosynthesis routes. According to the SRM proposal, glycine was the first amino acid encoded, followed by serine.
The coevolution model does not state precisely which the first encodings were, only presenting a list of about ten early assignments
including the derivation of glycine from serine—this being derived from the glycolysis intermediate glycerate, which reverses
the order proposed by the self-referential model. Our search identified the glycine-serine pathway of syntheses based on one-carbon
sources, involving activities of the glycine decarboxylase complex and its associated serine hydroxymethyltransferase, which
is consistent with the order proposed by the self-referential model and supports its rationale for the origin of the genetic
code: protein synthesis was developed inside an early metabolic system, serving the function of a sink of amino acids; the
first peptides were glycine-rich and fit for the function of building the early ribonucleoproteins; glycine consumption in
proteins drove the fixation of the glycine-serine pathway. 相似文献
20.
Gonalo C. Cardoso Brian T. Klingbeil Frank A. La Sorte Christopher A. Lepczyk Daniel Fink Curtis H. Flather 《Global Ecology and Biogeography》2020,29(8):1430-1434
The noise filter hypothesis predicts that species using higher sound frequencies should be more tolerant of noise pollution, because anthropogenic noise is more intense at low frequencies. Recent work analysed continental‐scale data on anthropogenic noise across the USA and found that passerine species inhabiting more noise‐polluted areas do not have higher peak song frequency but have more complex songs. However, this metric of song complexity is of ambiguous interpretation, because it can indicate either diverse syllables or a larger frequency bandwidth. In the latter case, the finding would support the noise filter hypothesis, because larger frequency bandwidths mean that more sound energy spreads to frequencies that are less masked by anthropogenic noise. We reanalysed how passerine song predicts exposure to noise using a more thorough dataset of acoustic song measurements, and showed that it is large frequency bandwidths, rather than diverse syllables, that predict the exposure of species to noise pollution. Given that larger bandwidths often encompass higher maximum frequencies, which are less masked by anthropogenic noise, our result suggests that tolerance to noise pollution might depend mostly on having the high‐frequency parts of song little masked by noise, thus preventing acoustic communication from going entirely unnoticed at long distances. 相似文献