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181.
Jon P. Costanzo Alice M. Reynolds M. Clara F. do Amaral Andrew J. Rosendale Richard E. Lee Jr. 《PloS one》2015,10(2)
Wood frogs (Rana sylvatica) exhibit marked geographic variation in freeze tolerance, with subarctic populations tolerating experimental freezing to temperatures at least 10-13 degrees Celsius below the lethal limits for conspecifics from more temperate locales. We determined how seasonal responses enhance the cryoprotectant system in these northern frogs, and also investigated their physiological responses to somatic freezing at extreme temperatures. Alaskan frogs collected in late summer had plasma urea levels near 10 μmol ml-1, but this level rose during preparation for winter to 85.5 ± 2.9 μmol ml-1 (mean ± SEM) in frogs that remained fully hydrated, and to 186.9 ± 12.4 μmol ml-1 in frogs held under a restricted moisture regime. An osmolality gap indicated that the plasma of winter-conditioned frogs contained an as yet unidentified osmolyte(s) that contributed about 75 mOsmol kg-1 to total osmotic pressure. Experimental freezing to –8°C, either directly or following three cycles of freezing/thawing between –4 and 0°C, or –16°C increased the liver’s synthesis of glucose and, to a lesser extent, urea. Concomitantly, organs shed up to one-half (skeletal muscle) or two-thirds (liver) of their water, with cryoprotectant in the remaining fluid reaching concentrations as high as 0.2 and 2.1 M, respectively. Freeze/thaw cycling, which was readily survived by winter-conditioned frogs, greatly increased hepatic glycogenolysis and delivery of glucose (but not urea) to skeletal muscle. We conclude that cryoprotectant accrual in anticipation of and in response to freezing have been greatly enhanced and contribute to extreme freeze tolerance in northern R. sylvatica. 相似文献
182.
Delio José Mora Laila Rigolin Fortunato Leonardo Eurípedes Andrade-Silva Kennio Ferreira-Paim Ivonete Helena Rocha Rakel Rocha Vasconcelos David Nascimento Silva-Teixeira Gabriel Antonio Nogueira Nascentes Mario León Silva-Vergara 《PloS one》2015,10(3)
Cryptococcal meningitis (CM) remains as common life-threatening AIDS-defining illness mainly in resource-limited settings. Previous reports suggested that baseline cytokine profiles can be associated to fungal burden and clinical outcome. This study aimed to evaluate the baseline cytokine profiles in AIDS patients with CM and its relation with the outcome at weeks 2 and 10. Thirty AIDS patients with CM diagnosed by cerebrospinal fluid (CSF) Cryptococcus neoformans positive culture, India ink stain and cryptococcal antigen test were prospectively evaluated. As controls, 56 HIV-infected patients without CM and 48 non-HIV individuals were included. Baseline CSF and sera levels of IL-2, IL-4, IL-8, IL-10, IL-12p40, IL-17A, INF-γ and TNF-α were measured by ELISA. Of 30 CM patients, 24 (80%) were male, median age of 38.1. The baseline CSF high fungal burden and positive blood culture were associated with a positive CSF culture at week 2 (p = 0.043 and 0.029). Most CSF and sera cytokines presented higher levels in CM patients than control subjects (p < 0.05). CSF levels of IL-8, IL-12p40, IL-17A, TNF-α, INF-γ and sera TNF-α were significantly higher among survivors at weeks 2 and 10 (p < 0.05). Patients with increased intracranial pression exhibited CSF IL-10 high levels and poor outcome at week 10 (p = 0.032). Otherwise, baseline CSF log10 IFN-γ and IL-17A were negatively correlated with fungal burden (r = -0.47 and -0.50; p = 0.0175 and 0.0094, respectively). The mortality rate was 33% (10/30) at week 2 and 57% (17/30) at week 10. The severity of CM and the advanced immunodeficiency at admission were related to a poor outcome in these patients. Otherwise, the predominant Th1 cytokines profile among survivors confirms its pivotal role to infection control and would be a prognostic marker in cryptococcal meningitis. 相似文献
183.
Macrophage tumoricidal activity relies, mainly, on the release of Tumor Necrosis
Factor alpha (TNFα) and/or on reactive oxygen or nitrogen intermediates. In
the present work, we investigated the cytotoxic activity of resident peritoneal
macrophages against L929 fibrosarcoma cell line in vitro and
in vivo. Resident macrophages lysed L929 cells in a mechanism
independent of TNFα and cell-to-cell contact. The cytotoxic activity was
largely dependent on nitric oxide (NO) release since treatment with L-NAME (NOS
inhibitor) inhibited L929 cells killing. Macrophages from mice with targeted deletion
of inducible NO synthase (iNOS) together with L929 cells produced less NO and
displayed lower, but still significant, tumoricidal activity. Notably, NO production
and tumor lysis were abolished in co-cultures with macrophages deficient in
Interferon Regulatory Factor, IRF-1. Importantly, the in vitro
findings were reproduced in vivo as IRF-1 deficient animals
inoculated i.p with L929 cells were extremely susceptible to tumor growth and their
macrophages did not produce NO, while WT mice killed L929 tumor cells and their
macrophages produced high levels of NO. Our results indicate that IRF-1 is a master
regulator of bi-directional interaction between macrophages and tumor cells. Overall,
IRF-1 was essential for NO production by co-cultures and macrophage tumoricidal
activity in vitro as well as for the control of tumor growth
in vivo. 相似文献
184.
Daniella Braz Parente Fernando Fernandes Paiva Jaime Araújo Oliveira Neto Lilian Machado-Silva Fatima Aparecida Ferreira Figueiredo Valeria Lanzoni Carlos Frederico Ferreira Campos Pedro Emmanuel Alvarenga Americano do Brasil Marilia de Brito Gomes Renata de Mello Perez Rosana Souza Rodrigues 《PloS one》2015,10(5)
ObjectiveTo evaluate the capability of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) to assess steatohepatitis and fibrosis determined by histopathology in type 2 diabetic patients.MethodsFifty-nine type 2 diabetic patients (49 women, 10 men; mean age, 54 ± 9 years) were submitted to liver biopsy for the evaluation of non-alcoholic fatty liver disease (NAFLD) and underwent DWI on a 3.0T MR system using 10 b values. Institutional approval and patient consent were obtained. Pure molecular-based (D), perfusion-related (D*), and vascular fraction (f) were calculated using a double exponential model and least squares curve fitting. D, D*, and f were compared between patients with and without steatohepatitis and between patients with and without fibrosis. The variables were compared by using the Ranksum test and Student t-test.ResultsSteatohepatitis was observed in 22 patients and fibrosis in 16 patients. A lower D median (0.70 s/mm2 vs. 0.83 s/mm2, p<0.05) and a lower D* median (34.39 s/mm2 vs. 45.23 s/mm2, p<0.05) were observed among those with steatohepatitis. A lower D median (0.70 s/mm2 vs. 0.82 s/mm2, p<0.05) and a lower D* median (35.01 s/mm2 vs. 44.76 s/mm2, p=0.05) were also observed among those with fibrosis.ConclusionIVIM-DWI has the potential to aid in the characterization of steatohepatitis and fibrosis. 相似文献
185.
Increased urine podocyte‐associated messenger RNAs in severe obesity are evidence of podocyte injury
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186.
Magna C. Paiva Marcelo P. ávila Mariana P. Reis Patrícia S. Costa Regina M. D. Nardi Andréa M. A. Nascimento 《PloS one》2015,10(6)
Bacteria are assumed to efficiently remove organic pollutants from sewage in sewage treatment plants, where antibiotic-resistance genes can move between species via mobile genetic elements known as integrons. Nevertheless, few studies have addressed bacterial diversity and class 1 integron abundance in tropical sewage. Here, we describe the extant microbiota, using V6 tag sequencing, and quantify the class 1 integron-integrase gene (intI1) in raw sewage (RS) and activated sludge (AS). The analysis of 1,174,486 quality-filtered reads obtained from RS and AS samples revealed complex and distinct bacterial diversity in these samples. The RS sample, with 3,074 operational taxonomic units, exhibited the highest alpha-diversity indices. Among the 25 phyla, Proteobacteria, Bacteroidetes and Firmicutes represented 85% (AS) and 92% (RS) of all reads. Increased relative abundance of Micrococcales, Myxococcales, and Sphingobacteriales and reduced pathogen abundance were noted in AS. At the genus level, differences were observed for the dominant genera Simplicispira and Diaphorobacter (AS) as well as for Enhydrobacter (RS). The activated sludge process decreased (55%) the amount of bacteria harboring the intI1 gene in the RS sample. Altogether, our results emphasize the importance of biological treatment for diminishing pathogenic bacteria and those bearing the intI1 gene that arrive at a sewage treatment plant. 相似文献
187.
Vanessa Carregaro José M. Ribeiro Jesus G. Valenzuela Djalma L. Souza-Júnior Diego L. Costa Carlo J. F. Oliveira Laís A. Sacramento Manuela S. L. Nascimento Cristiane M. Milanezi Fernando Q. Cunha Jo?o S. Silva 《PLoS neglected tropical diseases》2015,9(4)
Background
Sand fly saliva plays a crucial role in establishing Leishmania infection. We identified adenosine (ADO) and adenosine monophosphate (AMP) as active pharmacologic compounds present in Phlebotomus papatasi saliva that inhibit dendritic cell (DC) functions through a PGE2/IL 10-dependent mechanism.Methodology/Principal Findings
Herein, we prepared a mixture of ADO and AMP in equimolar amounts similar to those present in the salivary-gland extract (SGE) form one pair of salivary glands of P. papatasi and co-injected it with Leishmania amazonensis or L. major into mouse ears. ADO+AMP mimicked exacerbative effects of P. papatasi saliva in leishmaniasis, increasing parasite burden and cutaneous lesions. Enzymatic catabolism of salivary nucleosides reversed the SGE-induced immunosuppressive effect associated with IL-10 enhancement. Immunosuppressive factors COX2 and IL-10 were upregulated and failed to enhance ear lesion and parasite burden in IL 10-/- infected mice. Furthermore, nucleosides increased regulatory T cell (Treg) marker expression on CD4+CD25- cells, suggesting induction of Tregs on effector T cells (T eff). Treg induction (iTreg) was associated with nucleoside-induced tolerogenic dendritic cells (tDCs) expressing higher levels of COX2 and IL-10. In vitro generation of Tregs was more efficient in DCs treated with nucleosides. Suppressive effects of nucleosides during cutaneous leishmaniasis were mediated through an A2AR-dependent mechanism. Using BALB/c mice deficient in A2A ADO receptor (A2AR–/–), we showed that co-inoculated mice controlled infection, displaying lower parasite numbers at infection sites and reduced iTreg generation.Conclusion/Significance
We have demonstrated that ADO and AMP in P. papatasi saliva mediate exacerbative effects of Leishmania infection by acting preferentially on DCs promoting a tolerogenic profile in DCs and by generating iTregs in inflammatory foci through an A2AR mechanism. 相似文献188.
189.
Selective Cytotoxicity of 1,3,4-Thiadiazolium Mesoionic Derivatives on Hepatocarcinoma Cells (HepG2)
Gustavo Jabor Gozzi Amanda do Rocio Andrade Pires Glaucio Valdameri Maria Eliane Merlin Rocha Glaucia Regina Martinez Guilhermina Rodrigues Noleto Alexandra Acco Carlos Eduardo Alves de Souza Aurea Echevarria Camilla Moretto dos Reis Attilio Di Pietro Sílvia Maria Suter Correia Cadena 《PloS one》2015,10(6)
In this work, we evaluated the cytotoxicity of mesoionic 4-phenyl-5-(2-Y, 4-X or 4-X-cinnamoyl)-1,3,4-thiadiazolium-2-phenylamine chloride derivatives (MI-J: X=OH, Y=H; MI-D: X=NO2, Y=H; MI-4F: X=F, Y=H; MI-2,4diF: X=Y=F) on human hepatocellular carcinoma (HepG2), and non-tumor cells (rat hepatocytes) for comparison. MI-J, M-4F and MI-2,4diF reduced HepG2 viability by ~ 50% at 25 μM after 24-h treatment, whereas MI-D required a 50 μM concentration, as shown by 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. The cytotoxicity was confirmed with lactate dehydrogenase assay, of which activity was increased by 55, 24 and 16% for MI-J, MI-4F and MI-2,4diF respectively (at 25 μM after 24 h). To identify the death pathway related to cytotoxicity, the HepG2 cells treated by mesoionic compounds were labeled with both annexin V and PI, and analyzed by flow cytometry. All compounds increased the number of doubly-stained cells at 25 μM after 24 h: by 76% for MI-J, 25% for MI-4F and MI-2,4diF, and 11% for MI-D. It was also verified that increased DNA fragmentation occurred upon MI-J, MI-4F and MI-2,4diF treatments (by 12%, 9% and 8%, respectively, at 25 μM after 24 h). These compounds were only weakly, or not at all, transported by the main multidrug transporters, P-glycoprotein, ABCG2 and MRP1, and were able to slightly inhibit their drug-transport activity. It may be concluded that 1,3,4-thiadiazolium compounds, especially the hydroxy derivative MI-J, constitute promising candidates for future investigations on in-vivo treatment of hepatocellular carcinoma. 相似文献
190.
Michele Carbonelli Chiara La Morgia Giacomo Savini Maria Lucia Cascavilla Enrico Borrelli Filipe Chicani Carolina do V. F. Ramos Solange R. Salomao Vincenzo Parisi Jerry Sebag Francesco Bandello Alfredo A. Sadun Valerio Carelli Piero Barboni 《PloS one》2015,10(6)