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101.
Milena S. Espíndola Leonardo J. G. Lima Luana S. Soares Maira C. Cacemiro Fabiana A. Zambuzi Matheus de Souza Gomes Laurence R. Amaral Valdes R. Bollela Olindo A. Martins-Filho Fabiani G. Frantz 《PloS one》2015,10(12)
Background
Successful highly active antiretroviral therapy (HAART) has changed the outcome of AIDS patients worldwide because the complete suppression of viremia improves health and prolongs life expectancy of HIV-1+ patients. However, little attention has been given to the immunological profile of patients under distinct HAART regimens. This work aimed to investigate the differences in the immunological pattern of HIV-1+ patients under the first- or second-line HAART in Brazil.Methods
CD4+ T cell counts, Viral load, and plasma concentration of sCD14, sCD163, MCP-1, RANTES, IP-10, IL-1β, IL-6, TNF-α, IL-12, IFN-α, IFN-γ, IL-4, IL-5, and IL-10 were assessed for immunological characterization of the following clinical groups: Non-infected individuals (NI; n = 66), HIV-1+ untreated (HIV; n = 46), HIV-1+ treated with first-line HAART (HAART 1; n = 15); and HIV-1+ treated with second-line HAART (HAART 2; n = 15).Results
We found that the immunological biosignature pattern of HAART 1 is similar to that of NI individuals, especially in patients presenting slow progression of the disease, while patients under HAART 2 remain in a moderate inflammatory state, which is similar to that of untreated HIV patients pattern. Network correlations revealed that differences in IP-10, TNF-α, IL-6, IFN-α, and IL-10 interactions were primordial in HIV disease and treatment. Heat map and decision tree analysis identified that IP-10>TNF-α>IFN-α were the best respective HAART segregation biomarkers.Conclusion
HIV patients in different HAART regimens develop distinct immunological biosignature, introducing a novel perspective into disease outcome and potential new therapies that consider HAART patients as a heterogeneous group. 相似文献102.
Gary A. Clawson Gail L. Matters Ping Xin Yuka Imamura-Kawasawa Zhen Du Diane M. Thiboutot Klaus F. Helm Rogerio I. Neves Thomas Abraham 《PloS one》2015,10(8)
Background
While the morbidity and mortality from cancer are largely attributable to its metastatic dissemination, the integral features of the cascade are not well understood. The widely accepted hypothesis is that the primary tumor microenvironment induces the epithelial-to-mesenchymal transition in cancer cells, facilitating their escape into the bloodstream, possibly accompanied by cancer stem cells. An alternative theory for metastasis involves fusion of macrophages with tumor cells (MTFs). Here we culture and characterize apparent MTFs from blood of melanoma patients.Methods
We isolated enriched CTC populations from peripheral blood samples from melanoma patients, and cultured them. We interrogated these cultured cells for characteristic BRAF mutations, and used confocal microscopy for immunophenotyping, motility, DNA content and chromatin texture analyses, and then conducted xenograft studies using nude mice.Findings
Morphologically, the cultured MTFs were generally large with many pseudopod extensions and lamellipodia. Ultrastructurally, the cultured MTFs appeared to be macrophages. They were rich in mitochondria and lysosomes, as well as apparent melanosomes. The cultured MTF populations were all heterogeneous with regard to DNA content, containing aneuploid and/or high-ploidy cells, and they typically showed large sheets (and/or clumps) of cytoplasmic chromatin. This cytoplasmic DNA was found within heterogeneously-sized autophagic vacuoles, which prominently contained chromatin and micronuclei. Cultured MTFs uniformly expressed pan-macrophage markers (CD14, CD68) and macrophage markers indicative of M2 polarization (CD163, CD204, CD206). They also expressed melanocyte-specific markers (ALCAM, MLANA), epithelial biomarkers (KRT, EpCAM), as well as the pro-carcinogenic cytokine MIF along with functionally related stem cell markers (CXCR4, CD44). MTF cultures from individual patients (5 of 8) contained melanoma-specific BRAF activating mutations. Chromatin texture analysis of deconvoluted images showed condensed DNA (DAPI-intense) regions similar to focal regions described in stem cell fusions. MTFs were readily apparent in vivo in all human melanomas examined, often exhibiting even higher DNA content than the cultured MTFs. When cultured MTFs were transplanted subcutaneously in nude mice, they disseminated and produced metastatic lesions at distant sites.Conclusions and Hypothesis
Apparent MTFs are present in peripheral blood of patients with cutaneous melanomas, and they possess the ability to form metastatic lesions when transplanted into mice. We hypothesize that these MTFs arise at the periphery of primary tumors in vivo, that they readily enter the bloodstream and invade distant tissues, secreting cytokines (such as MIF) to prepare “niches” for colonization by metastasis initiating cells. 相似文献103.
Luiza Helena Urso Pitassi Pedro Paulo Vissotto de Paiva Diniz Diana Gerardi Scorpio Marina Rovani Drummond Bruno Grosselli Lania Maria Lourdes Barjas-Castro Rovilson Gilioli Silvia Colombo Stanley Sowy Edward B. Breitschwerdt William L. Nicholson Paulo Eduardo Neves Ferreira Velho 《PLoS neglected tropical diseases》2015,9(1)
Bartonella species are blood-borne, re-emerging organisms, capable of causing prolonged infection with diverse disease manifestations, from asymptomatic bacteremia to chronic debilitating disease and death. This pathogen can survive for over a month in stored blood. However, its prevalence among blood donors is unknown, and screening of blood supplies for this pathogen is not routinely performed. We investigated Bartonella spp. prevalence in 500 blood donors from Campinas, Brazil, based on a cross-sectional design. Blood samples were inoculated into an enrichment liquid growth medium and sub-inoculated onto blood agar. Liquid culture samples and Gram-negative isolates were tested using a genus specific ITS PCR with amplicons sequenced for species identification. Bartonella henselae and Bartonella quintana antibodies were assayed by indirect immunofluorescence. B. henselae was isolated from six donors (1.2%). Sixteen donors (3.2%) were Bartonella-PCR positive after culture in liquid or on solid media, with 15 donors infected with B. henselae and one donor infected with Bartonella clarridgeiae. Antibodies against B. henselae or B. quintana were found in 16% and 32% of 500 blood donors, respectively. Serology was not associated with infection, with only three of 16 Bartonella-infected subjects seropositive for B. henselae or B. quintana. Bartonella DNA was present in the bloodstream of approximately one out of 30 donors from a major blood bank in South America. Negative serology does not rule out Bartonella spp. infection in healthy subjects. Using a combination of liquid and solid cultures, PCR, and DNA sequencing, this study documents for the first time that Bartonella spp. bacteremia occurs in asymptomatic blood donors. Our findings support further evaluation of Bartonella spp. transmission which can occur through blood transfusions. 相似文献
104.
105.
Bruno J. Neves Rodolpho C. Braga José C. B. Bezerra Pedro V. L. Cravo Carolina H. Andrade 《PLoS neglected tropical diseases》2015,9(1)
Morbidity and mortality caused by schistosomiasis are serious public health problems in developing countries. Because praziquantel is the only drug in therapeutic use, the risk of drug resistance is a concern. In the search for new schistosomicidal drugs, we performed a target-based chemogenomics screen of a dataset of 2,114 proteins to identify drugs that are approved for clinical use in humans that may be active against multiple life stages of Schistosoma mansoni. Each of these proteins was treated as a potential drug target, and its amino acid sequence was used to interrogate three databases: Therapeutic Target Database (TTD), DrugBank and STITCH. Predicted drug-target interactions were refined using a combination of approaches, including pairwise alignment, conservation state of functional regions and chemical space analysis. To validate our strategy, several drugs previously shown to be active against Schistosoma species were correctly predicted, such as clonazepam, auranofin, nifedipine, and artesunate. We were also able to identify 115 drugs that have not yet been experimentally tested against schistosomes and that require further assessment. Some examples are aprindine, gentamicin, clotrimazole, tetrabenazine, griseofulvin, and cinnarizine. In conclusion, we have developed a systematic and focused computer-aided approach to propose approved drugs that may warrant testing and/or serve as lead compounds for the design of new drugs against schistosomes. 相似文献
106.
Occurrence of an invasive coral in the southwest Atlantic and comparison with a congener suggest potential niche expansion 下载免费PDF全文
Lélis A. Carlos‐Júnior Danilo M. Neves Newton P. U. Barbosa Timothy P. Moulton Joel C. Creed 《Ecology and evolution》2015,5(11):2162-2171
Tubastraea tagusensis, a coral native to the Galapagos Archipelago, has successfully established and invaded the Brazilian coast where it modifies native tropical rocky shore and coral reef communities. In order to understand the processes underlying the establishment of T. tagusensis, we tested whether Maxent, a tool for species distribution modeling, based on the native range of T. tagusensis correctly forecasted the invasion range of this species in Brazil. The Maxent algorithm was unable to predict the Brazilian coast as a suitable environment for the establishment of T. tagusensis. A comparison between these models and a principal component analysis (PCA) allowed us to examine the environmental dissimilarity between the two occupied regions (native and invaded) and to assess the species' occupied niche breadth. According to the PCA results, lower levels of chlorophyll‐a and nitrate on the Atlantic coast segregate the Brazilian and Galapagos environments, implying that T. tagusensis may have expanded its realized niche during the invasion process. We tested the possible realized niche expansion in T. tagusensis by assuming that Tubastraea spp. have similar fundamental niches, which was supported by exploring the environmental space of T. coccinea, a tropical‐cosmopolitan congener of T. tagusensis. We believe that the usage of Maxent should be treated with caution, especially when applied to biological invasion (or climate change) scenarios where the target species has a highly localized native (original) distribution, which may represent only a small portion of its fundamental niche, and therefore a violation of a SDM assumption. 相似文献
107.
Renan Idalencio Fabiana Kalichak Jo?o Gabriel Santos Rosa Tiago Acosta de Oliveira Gessi Koakoski Darlan Gusso Murilo Sander de Abreu Ana Cristina Varrone Giacomini Heloísa Helena de Alcantara Barcellos Angelo L. Piato Leonardo José Gil Barcellos 《PloS one》2015,10(10)
The presence of drugs and their metabolites in surface waters and municipal effluents has been reported in several studies, but its impacts on aquatic organisms are not yet well understood. This study investigated the effects of acute exposure to the antipsychotic risperidone on the stress and behavioral responses in zebrafish. It became clear that intermediate concentration of risperidone inhibited the hypothalamic-pituitary-interrenal axis and displayed anxiolytic-like effects in zebrafish. The data presented here suggest that the presence of this antipsychotic in aquatic environments can alter neuroendocrine and behavior profiles in zebrafish. 相似文献
108.
Ana Paula Ribeiro Silvia Maria Amado Jo?o Roberto Casanova Dinato Vitor Daniel Tessutti Isabel Camargo Neves Sacco 《PloS one》2015,10(9)
Aim/Hypothesis
The etiology of plantar fasciitis (PF) has been related to several risk factors, but the magnitude of the plantar load is the most commonly described factor. Although PF is the third most-common injury in runners, only two studies have investigated this factor in runners, and their results are still inconclusive regarding the injury stage.Objective
Analyze and compare the plantar loads and vertical loading rate during running of runners in the acute stage of PF to those in the chronic stage of the injury in relation to healthy runners.Methods
Forty-five runners with unilateral PF (30 acute and 15 chronic) and 30 healthy control runners were evaluated while running at 12 km/h for 40 meters wearing standardized running shoes and Pedar-X insoles. The contact area and time, maximum force, and force-time integral over the rearfoot, midfoot, and forefoot were recorded and the loading rate (20–80% of the first vertical peak) was calculated. Groups were compared by ANOVAs (p<0.05).Results
Maximum force and force-time integral over the rearfoot and the loading rate was higher in runners with PF (acute and chronic) compared with controls (p<0.01). Runners with PF in the acute stage showed lower loading rate and maximum force over the rearfoot compared to runners in the chronic stage (p<0.01).Conclusion
Runners with PF showed different dynamic patterns of plantar loads during running over the rearfoot area depending on the injury stage (acute or chronic). In the acute stage of PF, runners presented lower loading rate and forces over the rearfoot, possibly due to dynamic mechanisms related to pain protection of the calcaneal area. 相似文献109.
Gesilda F. Neves José R. F. Silva Renato B. Moraes Thiago S. Fernandes Bruno M. Tenorio Romildo A. Nogueira 《Acta biotheoretica》2014,62(2):133-143
The production, distribution and use of electricity can generate low frequency electric and magnetic fields (50–60 Hz). Considering that some studies showed adverse effects on pancreatic β-cells exposed to these fields; the present study aimed to analyze the effects of 60 Hz electric fields on membrane potential during the silent and burst phases in pancreatic β-cells using a mathematical model. Sinusoidal 60 Hz electric fields with amplitude ranging from 0.5 to 4 mV were applied on pancreatic β-cells model. The sinusoidal electric field changed burst duration, inter-burst intervals (silent phase) and spike sizes. The parameters above presented dose-dependent response with the voltage amplitude applied. In conclusion, theoretical analyses showed that a 60 Hz electric field with low amplitudes changes the membrane potential in pancreatic β-cells. 相似文献
110.