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961.
Dayvison Francis Saraiva Freitas Antonio Carlos Francesconi do Valle Margarete Bernardo Tavares da Silva Dayse Pereira Campos Marcelo Rosandiski Lyra Rogerio Valls de Souza Valdiléa Gon?alves Veloso Rosely Maria Zancopé-Oliveira Francisco Inácio Bastos Maria Clara Gutierrez Galhardo 《PLoS neglected tropical diseases》2014,8(8)
Sporotrichosis associated with zoonotic transmission remains a relevant public health problem in Rio de Janeiro, Brazil, affecting a large at-risk population, which includes HIV-infected individuals. We assessed patients co-infected by Sporothrix spp. and HIV over time in the context of an unabated sporotrichosis epidemic.A retrospective cohort retrieved information from a National reference institute for infectious diseases regarding 48 patients with sporotrichosis-HIV co-infection (group 1) as well as 3,570 patients with sporotrichosis (group 2), from 1987 through March 2013. Most patients from group 1 were male (68.8%), whereas women were predominant in group 2 (69.1%; p<0.0001). Patients from group 1 were younger than those from group 2 (μ = 38.38±10.17 vs. 46.34±15.85; p<0.001) and differed from group 2 in terms of their race/ethnic background, with 70.8% non-white patients in group 1 vs. 38.6% from group 2 (p<0.0001). Close to half (∼44%) of the patients from group 1 were hospitalized due to sporotrichosis over time, whereas hospitalization was very unlikely in group 2, among whom approximately 1% were hospitalized over time. Dissemination of sporotrichosis was the main cause of hospitalization in both groups, although it was more common among hospitalized patients from group 1 (19/21 [90.5%] vs. 16/37 [43.2%]; p<0.001). Over the period under analysis, eight patients died due to sporotrichosis (3/48 vs. 5/3,570). The diagnosis of sporotrichosis elicited HIV testing and subsequent diagnosis in 19/48 patients, whereas 23/48 patients were simultaneously diagnosed with the two infections.HIV infection aggravates sporotrichosis, with a higher incidence of severe disseminated cases and a higher number of hospitalizations and deaths. Underserved populations, among whom sporotrichosis has been propagated, have been affected by different transmissible (e.g., HIV) and non-transmissible diseases. These populations should be targeted by community development programs and entitled to integrated management and care of their superimposed burdens. 相似文献
962.
Yong He Robert Fisher Soma Chowdhury Ishrat Sultana Claudia P. Pereira Mike Bray Jennifer L. Reed 《PloS one》2014,9(11)
Rationale
Humans with a dominant negative mutation in STAT3 are susceptible to severe skin infections, suggesting an essential role for STAT3 signaling in defense against cutaneous pathogens.Methods
To focus on innate antiviral defenses in keratinocytes, we used a standard model of cutaneous infection of severe combined immunodeficient mice with the current smallpox vaccine, ACAM-2000. In parallel, early events post-infection with the smallpox vaccine ACAM-2000 were investigated in cultured keratinocytes of human and mouse origin.Results
Mice treated topically with a STAT3 inhibitor (Stattic) developed larger vaccinia lesions with higher virus titers and died more rapidly than untreated controls. Cultured human and murine keratinocytes infected with ACAM-2000 underwent rapid necrosis, but when treated with Stattic or with inhibitors of RIP1 kinase or caspase-1, they survived longer, produced higher titers of virus, and showed reduced activation of type I interferon responses and inflammatory cytokines release. Treatment with inhibitors of RIP1 kinase and STAT3, but not caspase-1, also reduced the inflammatory response of keratinocytes to TLR ligands. Vaccinia growth properties in Vero cells, which are known to be defective in some antiviral responses, were unaffected by inhibition of RIP1K, caspase-1, or STAT3.Conclusions
Our findings indicate that keratinocytes suppress the replication and spread of vaccinia virus by undergoing rapid programmed cell death, in a process requiring STAT3. These data offer a new framework for understanding susceptibility to skin infection in patients with STAT3 mutations. Interventions which promote prompt necroptosis/pyroptosis of infected keratinocytes may reduce risks associated with vaccination with live vaccinia virus. 相似文献963.
Michael Visser Sofiya N. Parshina Joana I. Alves Diana Z. Sousa Inês A. C. Pereira Gerard Muyzer Jan Kuever Alexander V. Lebedinsky Jasper J. Koehorst Petra Worm Caroline M. Plugge Peter J. Schaap Lynne A. Goodwin Alla Lapidus Nikos C. Kyrpides Janine C. Detter Tanja Woyke Patrick Chain Karen W. Davenport Stefan Spring Manfred Rohde Hans Peter Klenk Alfons J.M. Stams 《Standards in genomic sciences》2014,9(3):655-675
964.
Bianca Silva Vieira de Souza Karla Christina Sousa Silva Ana Flávia Alves Parente Clayton Luiz Borges Juliano Domiraci Paccez Maristela Pereira Célia Maria de Almeida Soares Marcia Giambiagi-deMarval Mirelle Garcia Silva-Bailão Juliana Alves Parente-Rocha 《Microbes and infection / Institut Pasteur》2019,21(10):456-463
Staphylococcus saprophyticus is a gram-positive coagulase negative bacteria which shows clinical importance due to its capability of causing urinary tract infections (UTI), as well as its ability to persist in this environment. Little is known about how S. saprophyticus adapts to the pH shift that occurs during infection. Thus, in this study we aim to use a proteomic approach to analyze the metabolic adaptations which occur as a response by S. saprophyticus when exposed to acid (5.5) and alkaline (9.0) pH environments. Proteins related to iron storage are overexpressed in acid pH, whilst iron acquisition proteins are overexpressed in alkaline pH. It likely occurs because iron is soluble at acid pH and insoluble at alkaline pH. To evaluate if S. saprophyticus synthesizes siderophores, CAS assays were performed, and the results confirmed their production. The chemical characterization of siderophores demonstrates that S. saprophyticus produces carboxylates derived from citrate. Of special note is the fact that citrate synthase (CS) is down-regulated during incubation at acid pH, corroborating this result. This data was also confirmed by enzymatic assay. Our results demonstrate that iron metabolism regulation is influenced by different pH levels, and show, for the first time, the production of siderophores by S. saprophyticus. Enzymatic assays suggest that citrate from the tricarboxylic acid cycle (TCA) is used as substrate for siderophore production. 相似文献
965.
A. C. Chaves N. Lucena-Silva F. G. C. Abath V. R. A. Pereira J. L. Lima-Filho A. L. F. Porto J. M. S. Cabral 《Bioprocess and biosystems engineering》2000,23(5):435-438
This work describes the partition of a Schistosoma mansoni tegumental antigen produced by a recombinant Escherichia coli strain using an aqueous two-phase system composed of polyethylene glycol (PEG) and potassium phosphate. The effects of the polymer molecular weight, tie line length and pH on antigen partitioning were investigated. The detection of the antigen in both phases were determined by ELISA. The system composed of PEG 3550 (19.7% w/w) and potassium phosphate (17.7% w/w) led to a yield of 59% and an antigen purification factor of 3 in the PEG-rich phase. It was observed that the antigen partition in ATPS was strongly affected by the pH value and tie line length. In addition, it was possible in a single step, to remove the cell debris, that precipitated at the interface of the system. 相似文献
966.
Carla Oliveira-Ribeiro Maria Inês Fernandes Pimentel Liliane de Ftima Antonio Oliveira rica de Camargo Ferreira e Vasconcellos Fatima Conceio-Silva Armando de Oliveira Schubach Aline Fagundes Cintia Xavier de Mello Eliame Mouta-Confort Luciana de Freitas Campos Miranda Claudia Maria Valete-Rosalino Ana Cristina da Costa Martins Raquel de Vasconcellos Carvalhaes de Oliveira Leonardo Pereira Quintella Marcelo Rosandiski Lyra 《PLoS neglected tropical diseases》2021,15(9)
BackgroundTreatment of cutaneous leishmaniasis (CL) remains challenging since the drugs currently used are quite toxic, thus contributing to lethality unrelated to the disease itself but to adverse events (AE). The main objective was to evaluate different treatment regimens with meglumine antimoniate (MA), in a reference center in Rio de Janeiro, Brazil.MethodologyA historical cohort of 592 patients that underwent physical and laboratory examination were enrolled between 2000 and 2017. The outcome measures of effectiveness were epithelialization and complete healing of cutaneous lesions. AE were graded using a standardized scale. Three groups were evaluated: Standard regimen (SR): intramuscular (IM) MA 10–20 mg Sb5+/kg/day during 20 days (n = 46); Alternative regimen (AR): IM MA 5 mg Sb5+/kg/day during 30 days (n = 456); Intralesional route (IL): MA infiltration in the lesion(s) through subcutaneous injections (n = 90). Statistical analysis was performed through Fisher exact and Pearson Chi-square tests, Kruskal-Wallis, Kaplan-Meier and log-rank tests.ResultsSR, AR and IL showed efficacy of 95.3%, 84.3% and 75.9%, with abandonment rate of 6.5%, 2.4% and 3.4%, respectively. IL patients had more comorbidities (58.9%; p = 0.001), were mostly over 50 years of age (55.6%), and had an evolution time longer than 2 months (65.6%; p = 0.02). Time for epithelialization and complete healing were similar in IL and IM MA groups (p = 0.9 and p = 0.5; respectively). Total AE and moderate to severe AE that frequently led to treatment interruption were more common in SR group, while AR and IL showed less toxicity.Conclusions/SignificanceAR and IL showed less toxicity and may be good options especially in CL cases with comorbidities, although SR treatment was more effective. IL treatment was an effective and safe strategy, and it may be used as first therapy option as well as a rescue scheme in patients initially treated with other drugs. 相似文献
967.
Cristina Snchez-Gonzlez Juan Cruz Herrero Martín Beat Salegi Ansa Cristina Núez de Arenas Brina Stan
i
Marta P. Pereira Laura Contreras Jos M. Cuezva Laura Formentini 《Cell death & disease》2022,13(6)
Tubular aggregates (TA) are honeycomb-like arrays of sarcoplasmic-reticulum (SR) tubules affecting aged glycolytic fibers of male individuals and inducing severe sarcomere disorganization and muscular pain. TA develop in skeletal muscle from Tubular Aggregate Myopathy (TAM) patients as well as in other disorders including endocrine syndromes, diabetes, and ageing, being their primary cause unknown. Nowadays, there is no cure for TA. Intriguingly, both hypoxia and calcium dyshomeostasis prompt TA formation, pointing to a possible role for mitochondria in their setting. However, a functional link between mitochondrial dysfunctions and TA remains unknown. Herein, we investigate the alteration in muscle-proteome of TAM patients, the molecular mechanism of TA onset and a potential therapy in a preclinical mouse model of the disease. We show that in vivo chronic inhibition of the mitochondrial ATP synthase in muscle causes TA. Upon long-term restrained oxidative phosphorylation (OXPHOS), oxidative soleus experiments a metabolic and structural switch towards glycolytic fibers, increases mitochondrial fission, and activates mitophagy to recycle damaged mitochondria. TA result from the overresponse of the fission controller DRP1, that upregulates the Store-Operate-Calcium-Entry and increases the mitochondria-SR interaction in a futile attempt to buffer calcium overloads upon prolonged OXPHOS inhibition. Accordingly, hypoxic muscles cultured ex vivo show an increase in mitochondria/SR contact sites and autophagic/mitophagic zones, where TA clusters grow around defective mitochondria. Moreover, hypoxia triggered a stronger TA formation upon ATP synthase inhibition, and this effect was reduced by the DRP1 inhibitor mDIVI. Remarkably, the muscle proteome of TAM patients displays similar alterations in mitochondrial dynamics and in ATP synthase contents. In vivo edaravone treatment in mice with restrained OXPHOS restored a healthy phenotype by prompting mitogenesis and mitochondrial fusion. Altogether, our data provide a functional link between the ATP synthase/DRP1 axis and the setting of TA, and repurpose edaravone as a possible treatment for TA-associated disorders.Subject terms: Musculoskeletal abnormalities, Energy metabolism 相似文献
968.
Flavio I. Bachini Danilo Pereira Ruan Santos Matheus Hausen Glauber Pereira Camila Vieira Lee Taylor Marcelle Pegurier 《Biology of sport / Institute of Sport》2022,39(3):745
Capillary dried blood spot (DBS) samples facilitate field-based collection without venipuncture. This pilot study aims to evaluate the viability of creatine (Cr) and creatinine (Crt) quantification using fresh capillary serum (CrS/CrtS) and DBS samples (CrDBS/CrtDBS), using Flow Injection Analysis Mass Spectrometry (FIA – MS). Nine Olympic Athletes provided a capillary blood sample to assess CrS/CrtS and CrDBS/CrtDBS quantified by FIA – MS. No difference between CrtS (mean ± SD: 813.6 ± 102.4 μmol/L) and CrtDBS (812.4 ± 108.1 μmol/L) was observed with acceptable variance [SEM 88.7; CV 10.7%; ICC 0.57 (CI 95% 0.06 – 0.84)] and agreement [very strong (Spearman: r = 0.77; p < 0.01) or strong (Pearson: r = 0.56; p = 0.04); Bland Altman: lower (-193) and upper (+196) limits of agreement]. CrS (mean ± SD: 691.8 ± 165.2 μmol/L) was significantly different to CrDBS (2911 ± 571.4 μmol/L) with unacceptable variance [SEM 171.6; CV 27%; ICC 0.002 (CI 95% -0.02 – 0.07)] and ‘weak’ agreement [Spearman: r = 0.21, p = 0.47 and Pearson: r = 0.06, p = 0.84; Bland Altman lower (-3367) and upper (-1072) limits of agreement]. Crt quantification is viable using both CrtS and CrtDBS (but not for Cr and CrS/CrDBS), with the DBS tissue handling technique offering several methodological and practice facing advantages. Future work should expand upon the sample size, explore sport/discipline relevant analytes across a full competitive season, including key training, recovery and performance blocks of their periodized performance plan. 相似文献
969.
970.
Colin C Demasi MA Degaki TL Bustos-Valenzuela JC Figueira RC Montor WR Cruz LO Lojudice FH Muras AG Pereira TM Winnischofer SM Hasegawa AP Carreira AC Verbisck NV Corrêa RG Garay-Malpartida HM Mares-Guia TR Corrêa-Giannella ML Granjeiro JM Sogayar MC 《Molecular biotechnology》2008,39(2):89-95
Social and economical development is closely associated with technological innovation and a well-developed biotechnological industry. In the last few years, Brazil’s scientific production has been steadily increasing; however, the number of patents is lagging behind, with technological and translational research requiring governmental incentive and reinforcement. The Cell and Molecular Therapy Center (NUCEL) was created to develop activities in the translational research field, addressing concrete problems found in biomedical and veterinary areas and actively searching for solutions by employing a genetic engineering approach to generate cell lines over-expressing recombinant proteins to be transferred to local biotech companies, aiming at furthering the development of a national competence for local production of biopharmaceuticals of widespread use and of life-saving importance. To this end, mammalian cell engineering technologies were used to generate cell lines over-expressing several different recombinant proteins of biomedical and biotechnological interest, namely, recombinant human Amylin/IAPP for diabetes treatment, human FVIII and FIX clotting factors for hemophilia, human and bovine FSH for fertility and reproduction, and human bone repair proteins (BMPs). Expression of some of these proteins is also being sought with the baculovirus/insect cell system (BEVS) which, in many cases, is able to deliver high-yield production of recombinant proteins with biological activity comparable to that of mammalian systems, but in a much more cost-effective manner. Transfer of some of these recombinant products to local Biotech companies has been pursued by taking advantage of the São Paulo State Foundation (FAPESP) and Federal Government (FINEP, CNPq) incentives for joint Research Development and Innovation partnership projects. 相似文献