全文获取类型
收费全文 | 3030篇 |
免费 | 202篇 |
出版年
2024年 | 4篇 |
2023年 | 7篇 |
2022年 | 25篇 |
2021年 | 52篇 |
2020年 | 45篇 |
2019年 | 63篇 |
2018年 | 67篇 |
2017年 | 55篇 |
2016年 | 77篇 |
2015年 | 141篇 |
2014年 | 159篇 |
2013年 | 226篇 |
2012年 | 290篇 |
2011年 | 248篇 |
2010年 | 170篇 |
2009年 | 155篇 |
2008年 | 209篇 |
2007年 | 213篇 |
2006年 | 188篇 |
2005年 | 149篇 |
2004年 | 147篇 |
2003年 | 143篇 |
2002年 | 138篇 |
2001年 | 29篇 |
2000年 | 18篇 |
1999年 | 29篇 |
1998年 | 30篇 |
1997年 | 19篇 |
1996年 | 23篇 |
1995年 | 17篇 |
1994年 | 17篇 |
1993年 | 12篇 |
1992年 | 5篇 |
1991年 | 9篇 |
1990年 | 7篇 |
1989年 | 6篇 |
1988年 | 5篇 |
1987年 | 3篇 |
1986年 | 2篇 |
1985年 | 4篇 |
1984年 | 4篇 |
1983年 | 5篇 |
1982年 | 5篇 |
1981年 | 3篇 |
1980年 | 1篇 |
1979年 | 3篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1974年 | 2篇 |
排序方式: 共有3232条查询结果,搜索用时 15 毫秒
61.
Alvaro A. Sandoval-Montiel Martha Zentella-de-Pi?a José L. Ventura-Gallegos Susana Frías-González Ambar López-Macay Alejandro Zentella-Dehesa 《PloS one》2013,8(6)
Background
Among NSAIDs acetyl salicylic acid remains as a valuable tool because of the variety of benefic prophylactic and therapeutic effects. Nevertheless, the molecular bases for these responses have not been complete understood. We explored the effect of acetyl salicylic acid on the heat shock response.Results
Peripheral blood mononuclear cells from rats challenged with acetyl salicylic acid presented a faster kinetics of expression of HSP-72 messenger RNA and protein in response to in vitro heat shock. This effect reaches its maximum 2 h after treatment and disappeared after 5 h. On isolated peripheral blood mononuclear cells from untreated rats, incubation with acetyl salicylic acid was ineffective to produce priming, but this effect was mimicked when the cells were incubated with the combination of H2O2+ ASA.Conclusions
Administration of acetyl salicylic acid to rats alters HSP-72 expression mechanism in a way that it becomes more efficient in response to in vitro heat shock. The fact that in vitro acetyl salicylic acid alone did not induce this priming effect implies that in vivo other signals are required. Priming could be reproduces in vitro with the combination of acetyl salicylic acid+H2O2. 相似文献62.
Laura Moles Marta Gómez Hans Heilig Gerardo Bustos Susana Fuentes Willem de Vos Leónides Fernández Juan M. Rodríguez Esther Jiménez 《PloS one》2013,8(6)
The establishment and succession of bacterial communities in infants may have a profound impact in their health, but information about the composition of meconium microbiota and its evolution in hospitalized preterm infants is scarce. In this context, the objective of this work was to characterize the microbiota of meconium and fecal samples obtained during the first 3 weeks of life from 14 donors using culture and molecular techniques, including DGGE and the Human Intestinal Tract Chip (HITChip) analysis of 16S rRNA amplicons. Culture techniques offer a quantification of cultivable bacteria and allow further study of the isolate, while molecular techniques provide deeper information on bacterial diversity. Culture and HITChip results were very similar but the former showed lower sensitivity. Inter-individual differences were detected in the microbiota profiles although the meconium microbiota was peculiar and distinct from that of fecal samples. Bacilli and other Firmicutes were the main bacteria groups detected in meconium while Proteobacteria dominated in the fecal samples. Culture technique showed that Staphylococcus predominated in meconium and that Enterococcus, together with Gram-negative bacteria such as Escherichia coli, Escherichia fergusonii, Klebsiella pneumoniae and Serratia marcescens, was more abundant in fecal samples. In addition, HITChip results showed the prevalence of bacteria related to Lactobacillus plantarum and Streptococcus mitis in meconium samples whereas those related to Enterococcus, Escherichia coli, Klebsiella pneumoniae and Yersinia predominated in the 3rd week feces. This study highlights that spontaneously-released meconium of preterm neonates contains a specific microbiota that differs from that of feces obtained after the first week of life. Our findings indicate that the presence of Serratia was strongly associated with a higher degree of immaturity and other hospital-related parameters, including antibiotherapy and mechanical ventilation. 相似文献
63.
Germinal J. Canto Alarcon Yezenia Rubio Venegas Luis Bojorquez Narvaez Oscar E. Pizano Martínez Leticia García Casanova Susana Sosa Gallegos Alejandro Nava Vargas Andrea M. Olvera Ramírez Feliciano Milian Suazo 《PloS one》2013,8(10)
“Test-and-slaughter” has been successful in industrialized countries to control and eradicate tuberculosis from cattle; however, this strategy is too expensive for developing nations, where the prevalence is especially high. Vaccination with the Calmette-Guérin (BCG) strain has been shown to protect against the development of lesions in vaccinated animals: mouse, cattle and wildlife species. In this study, the immune response and the pathology of vaccinated (BCG-prime and BCG prime-CFP-boosted) and unvaccinated (controls) calves were evaluated under experimental settings. A 106 CFU dose of the BCG strain was inoculated subcutaneously on the neck to two groups of ten animas each. Thirty days after vaccination, one of the vaccinated groups was boosted with an M. bovis culture filtrate protein (CFP). Three months after vaccination, the three groups of animals were challenged with 5×105 CFU via intranasal by aerosol with a field strain of M. bovis. The immune response was monitored throughout the study. Protection was assessed based on immune response (IFN-g release) prechallenge, presence of visible lesions in lymph nodes and lungs at slaughter, and presence of bacilli in lymph nodes and lung samples in histological analysis. Vaccinated cattle, either with the BCG alone or with BCG and boosted with CFP showed higher IFN-g response, fewer lesions, and fewer bacilli per lesion than unvaccinated controls after challenge. Animals with low levels of IFN-g postvaccine-prechallenge showed more lesions than animals with high levels. Results from this study support the argument that vaccination could be incorporated into control programs to reduce the incidence of TB in cattle in countries with high prevalence. 相似文献
64.
Gabriel Paiva Diogo Neves Proen?a Romeu Francisco Paula Verissimo Susana S. Santos Luís Fonseca Isabel M. O. Abrantes Paula V. Morais 《PloS one》2013,8(11)
Bacteria associated with the nematode Bursaphelenchus xylophilus, a pathogen of trees and the causal agent of pine wilt disease (PWD) may play a role in the disease. In order to evaluate their role (positive or negative to the tree), strains isolated from the track of nematodes from infected Pinus pinaster trees were screened, in vitro, for their nematicidal potential. The bacterial products, from strains more active in killing nematodes, were screened in order to identify and characterize the nematicidal agent. Forty-seven strains were tested and, of these, 21 strains showed capacity to produce extracellular products with nematicidal activity. All Burkholderia strains were non-toxic. In contrast, all Serratia strains except one exhibited high toxicity. Nematodes incubated with Serratia strains showed, by SEM observation, deposits of bacteria on the nematode cuticle. The most nematicidal strain, Serratia sp. A88copa13, produced proteases in the supernatant. The use of selective inhibitors revealed that a serine protease with 70 kDa was majorly responsible for the toxicity of the supernatant. This extracellular serine protease is different phylogenetically, in size and biochemically from previously described proteases. Nematicidal assays revealed differences in nematicidal activity of the proteases to different species of Bursaphelenchus, suggesting its usefulness in a primary screen of the nematodes. This study offers the basis for further investigation of PWD and brings new insights on the role bacteria play in the defense of pine trees against B. xylophilus. Understanding all the factors involved is important in order to develop strategies to control B. xylophilus dispersion. 相似文献
65.
Jan F. Kamler Khamtai Thatdokkham Susana Rostro-García Anita Bousa Anthony Caragiulo Rachel Crouthers Visattha In Chen Pay Chanratana Pin Sovanna Prum Chantavy Vongkhamheng Arlyne Johnson David W. Macdonald 《The Journal of wildlife management》2020,84(7):1396-1405
Endangered dholes (Cuon alpinus) are restricted to small and declining populations in Southeast Asia, and little is known about how their ecology differs within the region. We used DNA-confirmed scats and prey surveys to determine the seasonal diet and prey selection of dholes in 2 different landscapes that dominate Southeast Asia: closed evergreen forests in hilly terrain in northern Laos, and open deciduous forests in relatively flat terrain in eastern Cambodia. On both sites, muntjac (Muntiacus spp.; 20–28 kg) was the dominant prey item and was selectively consumed over other ungulates in all seasons. Our findings differ from previous conclusions, based largely on studies from India, that the preferred prey weight range of dholes was either 40–60 kg or 130–190 kg. Other important prey were sambar (Rusa unicolor) in Laos, and wild pig (Sus scrofa) and banteng (Bos javanicus) in Cambodia. Seasonal differences in overall diet occurred in Laos, but not Cambodia, primarily because of an increase in livestock consumption. The mean number of dhole scats in group defecation sites was higher in Cambodia (5.9 ± 0.5 [SE]) than Laos (2.4 ± 0.2), suggesting pack sizes were larger in Cambodia. Our results suggest that regardless of land cover type, prey diversity, or pack size, the management of muntjac will be important for conserving dhole populations in Southeast Asia. In Laos, we recommend that local villagers remove livestock from the protected area during the hot-dry season to reduce livestock predation by dholes. © 2020 The Authors. The Journal of Wildlife Management published by Wiley Periodicals LLC on behalf of The Wildlife Society. 相似文献
66.
Hernández-Ledesma Ana Laura Rodríguez-Méndez Adriana Jheny Gallardo-Vidal Lilia Susana García-Gasca Teresa Alatorre-Cruz Julia María García-Solís Pablo López Reyes Julián Solís-Saínz Juan Carlos 《Molecular biology reports》2020,47(12):9667-9676
Molecular Biology Reports - Although cognitive impairment (CI) is classically associated with aging, it has been proposed that neurological pathologies may increase the risk to suffer CI. Despite... 相似文献
67.
Susana Solá Ana L. Morgado Cecília M.P. Rodrigues 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
Stem cell therapy is a strategy far from being satisfactory and applied in the clinic. Poor survival and differentiation levels of stem cells after transplantation or neural injury have been major problems. Recently, it has been recognized that cell death-relevant proteins, notably those that operate in the core of the executioner apoptosis machinery are functionally involved in differentiation of a wide range of cell types, including neural cells.Scope of review
This article will review recent studies on the mechanisms underlying the non-apoptotic function of mitochondrial and death receptor signaling pathways during neural differentiation. In addition, we will discuss how these major apoptosis-regulatory pathways control the decision between differentiation, self-renewal and cell death in neural stem cells and how levels of activity are restrained to prevent cell loss as final outcome.Major conclusions
Emerging evidence suggests that, much like p53, caspases and Bcl-2 family members, the two prime triggers of cell death pathways, death receptors and mitochondria, may influence proliferation and differentiation potential of stem cells, neuronal plasticity, and astrocytic versus neuronal stem cell fate decision.General significance
A better understanding of the molecular mechanisms underlying key checkpoints responsible for neural differentiation as an alternative to cell death will surely contribute to improve neuro-replacement strategies. 相似文献68.
69.
Susana Isabel Ferreira Luís Miguel Pires José Ferrão Joaquim Sá Armando Serra Isabel Marques Carreira 《Gene》2013
Fragile X syndrome is caused by the expansion of an unstable CGG repeat in the 5′UTR of FMR1 gene. The occurrence of mosaicism is not uncommon, especially in male patients, whereas in females it is not so often reported. Here we report a female foetus that was subject to prenatal diagnosis, because of her mother being a premutation carrier. The foetus was identified as being a mosaic for an intermediate allele and a full mutation of FMR1 gene, in the presence of a normal allele. The mosaic status was confirmed in three different tissues of the foetus – amniotic fluid, skin biopsy and blood – the last two obtained after pregnancy termination. Karyotype analysis and X-chromosome STR markers analysis do not support the mosaicism as inheritance of both maternal alleles. Oligonucleotide array-CGH excluded an imbalance that could contain the primer binding site with a different repeat size. The obtained results give compelling evidence for a postzygotic expansion mechanism where the foetus mosaic pattern originated from expansion of the mother's premutation into a full mutation and consequent regression to an intermediate allele in a proportion of cells. These events occurred in early embryogenesis before the commitment of cells into the different tissues, as the three tested tissues of the foetus have the same mosaic pattern. The couple has a son with Fragile X mental retardation syndrome and choose to terminate this pregnancy after genetic counselling. 相似文献
70.
Marcela A. Garabalino Elisa M. Heber Andrea Monti Hughes Sara J. González Ana J. Molinari Emiliano C. C. Pozzi Susana Nievas Maria E. Itoiz Romina F. Aromando David W. Nigg William Bauer Verónica A. Trivillin Amanda E. Schwint 《Radiation and environmental biophysics》2013,52(3):351-361
Boron neutron capture therapy (BNCT) is based on selective accumulation of 10B carriers in tumor followed by neutron irradiation. We previously proved the therapeutic success of BNCT mediated by the boron compounds boronophenylalanine and sodium decahydrodecaborate (GB-10) in the hamster cheek pouch oral cancer model. Based on the clinical relevance of the boron carrier sodium borocaptate (BSH) and the knowledge that the most effective way to optimize BNCT is to improve tumor boron targeting, the specific aim of this study was to perform biodistribution studies of BSH in the hamster cheek pouch oral cancer model and evaluate the feasibility of BNCT mediated by BSH at nuclear reactor RA-3. The general aim of these studies is to contribute to the knowledge of BNCT radiobiology and optimize BNCT for head and neck cancer. Sodium borocaptate (50 mg 10B/kg) was administered to tumor-bearing hamsters. Groups of 3–5 animals were killed humanely at nine time-points, 3–12 h post-administration. Samples of blood, tumor, precancerous pouch tissue, normal pouch tissue and other clinically relevant normal tissues were processed for boron measurement by optic emission spectroscopy. Tumor boron concentration peaked to therapeutically useful boron concentration values of 24–35 ppm. The boron concentration ratio tumor/normal pouch tissue ranged from 1.1 to 1.8. Pharmacokinetic curves showed that the optimum interval between BSH administration and neutron irradiation was 7–11 h. It is concluded that BNCT mediated by BSH at nuclear reactor RA-3 would be feasible. 相似文献