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91.
Nancy Argüelles Eugenia Sánchez-Sandoval Aarón Mendieta Lourdes Villa-Tanaca Leticia Garduño-Siciliano Fabiola Jiménez María del Carmen Cruz José L. Medina-Franco Germán Chamorro-Cevallos Joaquín Tamariz 《Bioorganic & medicinal chemistry》2010,18(12):4238-4248
A series of α-asarone-based analogues was designed by conducting docking experiments with published crystal structures of human HMG-CoA reductase. Indeed, synthesis and evaluation of this series showed a highly hypocholesterolemic in vivo activity in a murine model, as predicted by previous docking studies. In agreement with this model, the polar groups attached to the benzene ring could play a key role in the enzyme binding and probably also in its biological activity, mimicking the HMG-moiety of the natural substrate. The hypolipidemic action mechanism of these compounds was investigated by developing a simple, efficient, and novel model for determining HMG-CoA reductase inhibition. The partial purification of the enzyme from Schizosaccharomyces pombe allowed for testing of α-asarone- and fibrate-based analogues, resulting in positive and significant inhibitory activity. 相似文献
92.
The clinical application of amphotericin B (AmB), a broad spectrum antifungal agent, is limited by its poor solubility in aqueous medium and also by its proven renal toxicity. In this work, AmB was encapsulated in micelles obtained from the self-assembly of PDMAEMA-b-PCL-b-PDMAEMA triblock copolymers. The amount of encapsulated AmB depended on the copolymer composition, and short blocks of polycaprolactone (PCL) and poly(2-dimethylaminoethyl methacrylate) (PDMAEMA) showed better performance. All the studied formulations exhibited a controlled release of AmB along 150 h. The formulations presented reduced hemotoxicity while maintaining antifungal activities against Candida albicans, Candida krusei, and Candida glabrata comparable with free AmB. A reduction on the hemotoxicity was found to be due to the slow release and subsequent low aggregation achieved with the use of polymer micelle nanocontainers.KEY WORDS: amphotericin B, antifungal agent, hemotoxicity, micelles 相似文献
93.
María F. Garcés Elizabeth Sanchez Luisa F. Cardona Elkin L. Simanca Iván González Luis G. Leal José A. Mora Andrés Bedoya Juan P. Alzate ángel Y. Sánchez Javier H. Eslava-Schmalbach Roberto Franco-Vega Mario O. Parra Ariel I. Ruíz—Parra Carlos Diéguez Rubén Nogueiras Jorge E. Caminos 《PloS one》2015,10(6)
Background
Meteorin (METRN) is a recently described neutrophic factor with angiogenic properties. This is a nested case-control study in a longitudinal cohort study that describes the serum profile of METRN during different periods of gestation in healthy and preeclamptic pregnant women. Moreover, we explore the possible application of METRN as a biomarker.Methods and Findings
Serum METRN was measured by ELISA in a longitudinal prospective cohort study in 37 healthy pregnant women, 16 mild preeclamptic women, and 20 healthy non-pregnant women during the menstrual cycle with the aim of assessing serum METRN levels and its correlations with other metabolic parameters. Immunostaining for METRN protein was performed in placenta. A multivariate logistic regression model was proposed and a classifier model was formulated for predicting preeclampsia in early and middle pregnancy. The performance in classification was evaluated using measures such as sensitivity, specificity, and the receiver operating characteristic (ROC) curve. In healthy pregnant women, serum METRN levels were significantly elevated in early pregnancy compared to middle and late pregnancy. METRN levels are significantly lower only in early pregnancy in preeclamptic women when compared to healthy pregnant women. Decision trees that did not include METRN levels in the first trimester had a reduced sensitivity of 56% in the detection of preeclamptic women, compared to a sensitivity of 69% when METRN was included.Conclusions
The joint measurements of circulating METRN levels in the first trimester and systolic blood pressure and weight in the second trimester significantly increase the probabilities of predicting preeclampsia. 相似文献94.
Giulliana T. Almeida Regina C. G. Lage Leticia Anderson Thiago M. Venancio Helder I. Nakaya Patrícia A. Miyasato Henrique K. Rofatto Adhemar Zerlotini Eliana Nakano Guilherme Oliveira Sergio Verjovski-Almeida 《PLoS neglected tropical diseases》2015,9(9)
BackgroundTreatment and morbidity control of schistosomiasis relies on a single drug, praziquantel (PZQ), and the selection of resistant worms under repeated treatment is a concern. Therefore, there is a pressing need to understand the molecular effects of PZQ on schistosomes and to investigate alternative or synergistic drugs against schistosomiasis.MethodologyWe used a custom-designed Schistosoma mansoni expression microarray to explore the effects of sublethal doses of PZQ on large-scale gene expression of adult paired males and females and unpaired mature females. We also assessed the efficacy of PZQ, omeprazole (OMP) or their combination against S. mansoni adult worms with a survival in vitro assay.ConclusionsFunctional analysis of gene interaction networks is an important approach that can point to possible novel synergistic drug candidates. We demonstrated the potential of this strategy by showing that PZQ in combination with OMP displayed increased efficiency against S. mansoni adult worms in vitro when compared with either drug alone. 相似文献
95.
The gastrointestinal tract constitutes a physiological interface integrating nutrient and microbiota-host metabolism. Conjugated linoleic acids (CLA) have been reported to contribute to decreased body weight and fat accretion. The modulation by dietary CLA of stomach proteins related to energy homeostasis or microbiota may be involved, although this has not been previously analysed. This is examined in the present study, which aims to underline the potential mechanisms of CLA which contribute to body weight regulation. Adult mice were fed either a normal fat (NF, 12% kJ content as fat) or a high-fat (HF, 43% kJ content as fat) diet. In the latter case, half of the animals received daily oral supplementation of CLA. Expression and content of stomach proteins and specific bacterial populations from caecum were analysed. CLA supplementation was associated with an increase in stomach protein expression, and exerted a prebiotic action on both Bacteroidetes/Prevotella and Akkermansia muciniphila. However, CLA supplementation was not able to override the negative effects of HF diet on Bifidobacterium spp., which was decreased in both HF and HF+CLA groups. Our data show that CLA are able to modulate stomach protein expression and exert a prebiotic effect on specific gut bacterial species. 相似文献
96.
Lorena Garaicoechea Andrea Aguilar Gabriel I. Parra Marina Bok Stanislav V. Sosnovtsev Gabriela Canziani Kim Y. Green Karin Bok Viviana Parre?o 《PloS one》2015,10(8)
Noroviruses are a major cause of acute gastroenteritis, but no vaccines or therapeutic drugs are available. Llama-derived single chain antibody fragments (also called VHH) are small, recombinant monoclonal antibodies of 15 kDa with several advantages over conventional antibodies. The aim of this study was to generate recombinant monoclonal VHH specific for the two major norovirus (NoV) genogroups (GI and GII) in order to investigate their potential as immunotherapy for the treatment of NoV diarrhea. To accomplish this objective, two llamas were immunized with either GI.1 (Norwalk-1968) or GII.4 (MD2004) VLPs. After immunization, peripheral blood lymphocytes were collected and used to generate two VHH libraries. Using phage display technology, 10 VHH clones specific for GI.1, and 8 specific for GII.4 were selected for further characterization. All VHH recognized conformational epitopes in the P domain of the immunizing VP1 capsid protein, with the exception of one GII.4 VHH that recognized a linear P domain epitope. The GI.1 VHHs were highly specific for the immunizing GI.1 genotype, with only one VHH cross-reacting with GI.3 genotype. The GII.4 VHHs reacted with the immunizing GII.4 strain and showed a varying reactivity profile among different GII genotypes. One VHH specific for GI.1 and three specific for GII.4 could block the binding of homologous VLPs to synthetic HBGA carbohydrates, saliva, and pig gastric mucin, and in addition, could inhibit the hemagglutination of red blood cells by homologous VLPs. The ability of Nov-specific VHHs to perform well in these surrogate neutralization assays supports their further development as immunotherapy for NoV treatment and immunoprophylaxis. 相似文献
97.
Marcela Parra Xia Liu Steven C. Derrick Amy Yang Alvaro Molina-Cruz Carolina Barillas-Mury Hong Zheng Phuong Thao Pham Martha Sedegah Arnel Belmonte Dianne D. Litilit Thomas A. Waldmann Sanjai Kumar Sheldon L. Morris Liyanage P. Perera 《PloS one》2015,10(10)
Malaria remains a major global public health problem with an estimated 200 million cases detected in 2012. Although the most advanced candidate malaria vaccine (RTS,S) has shown promise in clinical trials, its modest efficacy and durability have created uncertainty about the impact of RTS,S immunization (when used alone) on global malaria transmission. Here we describe the development and characterization of a novel modified vaccinia virus Ankara (MVA)–based malaria vaccine which co-expresses the Plasmodium yoelii circumsporozoite protein (CSP) and IL-15. Vaccination/challenge studies showed that C57BL/6 mice immunized with the MVA-CSP/IL15 vaccine were protected significantly better against a P. yoelii 17XNL sporozoite challenge than either mice immunized with an MVA vaccine expressing only CSP or naïve controls. Importantly, the levels of total anti-CSP IgG were elevated about 100-fold for the MVA-CSP/IL15 immunized group compared to mice immunized with the MVA-CSP construct that does not express IL-15. Among the IgG subtypes, the IL-15 expressing MVA-CSP vaccine induced levels of IgG1 (8 fold) and IgG2b (80 fold) higher than the MVA-CSP construct. The significantly enhanced humoral responses and protection detected after immunization with the MVA-CSP/IL15 vaccine suggest that this IL-15 expressing MVA construct could be considered in the development of future malaria immunization strategies. 相似文献
98.
María Isabel Burgos Alves Francisco Avilés Plaza Rebeca Martínez-Tomás María Sánchez-Campillo Elvira Larqué Francisca Pérez-Llamas Pedro Martínez Hernández Soledad Parra Pallarés 《Journal of physiology and biochemistry》2010,66(3):221-227
The biological effects of oxidized LDL (oxLDL) may contribute to initiation and progression of the atherosclerotic process,
and the association between cardiovascular disease and oxidation of LDL has been largely demonstrated. The objectives of this
study were to establish the reference values of oxidative stress biomarkers in a young healthy Spanish population to determine
the concentration of oxLDL and its relationship with lipid profile and with these biomarkers. oxLDL, F2-isoprostanes, protein carbonyls (PC), and 8-hydroxy-2′-deoxyguanosine (8-OHdG) were determinate by ELISA in 72 healthy subjects.
Antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) were carried
out on a Hitachi 912 analyzer; lipid profile were assayed using automated systems (Cobas 711, Roche Diagnostics). All statistics
were analyzed by using SPSS for Windows 15.0. SPSS Inc, Chicago, IL, USA. (Normal mean reference values): oxLDL (63.23 ± 16.23
U/L), (Male/Female 68.06 ± 17.69/58.39 ± 13.6 U/L), F2-isoprostanes (2.26 ± 0.9 μg/g creatinine), PC (0.34 ± 0.15 nmol/mg), 8-OHdG (23.27 ± 10.58 ng/ml), SOD (931.97 ± 271.09 U/g
Hb), GR (46.56 ± 11.68 U/L), GPx (27.58 ± 6.89 U/gHb (Male/Female 25.91 ± 5.03/29.2 ± 8.07 U/L)). OxLDL (63.23 U/L) was significantly
(p < 0.05) positively correlated with BMI (22.53 Kg/m2), total cholesterol (175.79 mg/dl), triglycerides (87.58 mg/dl), LDL cholesterol (96.25 mg/dl), and uric acid (4.78 mg/dl),
while negatively correlated with HDL-cholesterol (62.25 mg/dl). We have found different correlation between oxLDL and isoprostanes
by gender with the rest of parameters. Normal reference values have been found significantly different for oxLDL and GPx by
gender. Oxidized LDL is correlated with lipid profile but not with the oxidative stress biomarkers. Urinary isoprostanes are
positively correlated with triglycerides and negatively with GR and GPx. 相似文献
99.
Luciane A. Faine Danielle M.H. Cavalcanti Martina Rudnicki Simone Ferderbar Sandra M.D. Macedo Heraldo P. Souza Sandra H.P. Farsky Lisardo Boscá Dulcineia Saes Parra Abdalla 《The Journal of nutritional biochemistry》2010,21(2):125-132
The vascular effects of nitrolinoleate (LNO2), an endogenous product of linoleic acid (LA) nitration by nitric oxide-derived species and a potential nitrosating agent, were investigated on rat endothelial-leukocyte interactions. Confocal microscopy analysis demonstrated that LNO2 was capable to deliver free radical nitric oxide (·NO) into cells, 5 min after its administration to cultured cells, with a peak of liberation at 30 min. THP-1 monocytes incubated with LNO2 for 5 min presented nitrosation of CD40, leading to its inactivation. Other anti-inflammatory actions of LNO2 were observed in vivo by intravital microscopy assays. LNO2 decreased the number of adhered leukocytes in postcapillary venules of the mesentery network. In addition to this, LNO2 reduced mRNA and protein expression of β2-integrin in circulating leukocytes, as well as VCAM-1 in endothelial cells isolated from postcapillary venules, confirming its antiadhesive effects on both cell types. Moreover, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, a nitric oxide scavenger, partially abolished the inhibitory action of LNO2 on leukocyte-endothelium interaction, suggesting that the antiadhesion effects of LNO2 involve a dual role in leukocyte adhesion, acting as a nitric oxide donor as well as through nitric oxide-independent mechanisms. In conclusion, LNO2 inhibited adhesion molecules expression and promoted ·NO inactivation of the CD40–CD40L system, both important processes of the inflammatory response. 相似文献
100.
Three 2,3‐dihydro‐1H‐isoindol‐1‐ones structurally related with piracetam (=2‐oxopyrrolidine‐1‐acetamide) have been synthesized and tested for their nootropic effects in the passive avoidance test in mice. Compounds (RS)‐ 2 , (R,R)‐ 3 , and (R,S)‐ 3 were obtained in good yields in only two steps starting from methyl dl ‐phthaloylalanine. Compound (RS)‐ 2 exhibited nootropic activity at lower doses than piracetam, used as reference drug, but it showed lower efficacy. Whereas diastereoisomers (R,R)‐ 3 and (R,S)‐ 3 were as potent as piracetam to revert amnesia induced by scopolamine, (R,S)‐ 3 showed lower efficacy than (R,R)‐ 3 . Only (R,R)‐ 3 showed myorelaxant effect at doses of 10 and 30 mg/kg; other compounds did not exhibit any anticonvulsant, sedative, myorelaxant, or impaired motor‐coordination effect in mice. These synthesized 2,3‐dihydro‐1H‐isoindol‐1‐one derivatives constitute a new kind of nootropic compounds. 相似文献