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101.
102.
Kathleen D'Halluin Chantal Vanderstraeten Jolien Van Hulle Joanna Rosolowska Ilse Van Den Brande Anouk Pennewaert Kristel D'Hont Martine Bossut Derek Jantz Rene Ruiter Jean Broadhvest 《Plant biotechnology journal》2013,11(8):933-941
Recent developments of tools for targeted genome modification have led to new concepts in how multiple traits can be combined. Targeted genome modification is based on the use of nucleases with tailor‐made specificities to introduce a DNA double‐strand break (DSB) at specific target loci. A re‐engineered meganuclease was designed for specific cleavage of an endogenous target sequence adjacent to a transgenic insect control locus in cotton. The combination of targeted DNA cleavage and homologous recombination–mediated repair made precise targeted insertion of additional trait genes (hppd, epsps) feasible in cotton. Targeted insertion events were recovered at a frequency of about 2% of the independently transformed embryogenic callus lines. We further demonstrated that all trait genes were inherited as a single genetic unit, which will simplify future multiple‐trait introgression. 相似文献
103.
Sylvaine You Luca Piali Chantal Kuhn Beat Steiner Virginia Sauvaget Fabrice Valette Martine Clozel Jean-Fran?ois Bach Lucienne Chatenoud 《PloS one》2013,8(10)
In the present study, we investigated the therapeutic potential of a selective S1P1 receptor modulator, ponesimod, to protect and reverse autoimmune diabetes in non-obese diabetic (NOD) mice. Ponesimod was administered orally to NOD mice starting at 6, 10, 13 and 16 weeks of age up to 35 weeks of age or to NOD mice showing recent onset diabetes. Peripheral blood and spleen B and T cell counts were significantly reduced after ponesimod administration. In pancreatic lymph nodes, B lymphocytes were increased and expressed a transitional 1-like phenotype. Chronic oral ponesimod treatment efficiently prevented autoimmune diabetes in 6, 10 and 16 week-old pre-diabetic NOD mice. Treatment withdrawal led to synchronized disease relapse. Ponesimod did not inhibit the differentiation of autoreactive T cells as assessed by adoptive transfer of lymphocytes from treated disease-free NOD mice. In addition, it did not affect the migration, proliferation and activation of transgenic BDC2.5 cells into the target tissue. However, ponesimod inhibited spreading of the T cell responses to islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP). Treatment of diabetic NOD mice with ponesimod induced disease remission. However, here again, upon treatment cessation, the disease rapidly recurred. This recurrence was effectively prevented by combination treatment with a CD3 antibody leading to the restoration of self-tolerance. In conclusion, treatment with a selective S1P1 modulator in combination with CD3 antibody represents a promising therapeutic approach for the treatment of autoimmune diabetes. 相似文献
104.
Joost F. von Schmidt auf Altenstadt Chantal W. P. M. Hukkelhoven Jos van Roosmalen Kitty W. M. Bloemenkamp 《PloS one》2013,8(12)
Background
Postpartum haemorrhage is a leading cause of maternal morbidity and mortality worldwide. Identifying risk indicators for postpartum haemorrhage is crucial to predict this life threatening condition. Another major contributor to maternal morbidity and mortality is pre-eclampsia. Previous studies show conflicting results in the association between pre-eclampsia and postpartum haemorrhage. The primary objective of this study was to investigate the association between pre-eclampsia and postpartum haemorrhage. Our secondary objective was to identify other risk indicators for postpartum haemorrhage in the Netherlands.Methods
A nationwide cohort was used, containing prospectively collected data of women giving birth after 19 completed weeks of gestation from January 2000 until January 2008 (n = 1 457 576). Data were extracted from the Netherlands Perinatal Registry, covering 96% of all deliveries in the Netherlands. The main outcome measure, postpartum haemorrhage, was defined as blood loss of ≥1000 ml in the 24 hours following delivery. The association between pre-eclampsia and postpartum haemorrhage was investigated with uni- and multivariable logistic regression analyses.Results
Overall prevalence of postpartum haemorrhage was 4.3% and of pre-eclampsia 2.2%. From the 31 560 women with pre-eclampsia 2 347 (7.4%) developed postpartum haemorrhage, compared to 60 517 (4.2%) from the 1 426 016 women without pre-eclampsia (odds ratio 1.81; 95% CI 1.74 to 1.89). Risk of postpartum haemorrhage in women with pre-eclampsia remained increased after adjusting for confounders (adjusted odds ratio 1.53; 95% CI 1.46 to 1.60).Conclusion
Women with pre-eclampsia have a 1.53 fold increased risk for postpartum haemorrhage. Clinicians should be aware of this and use this knowledge in the management of pre-eclampsia and the third stage of labour in order to reach the fifth Millenium Developmental Goal of reducing maternal mortality ratios with 75% by 2015. 相似文献105.
106.
Emilie Pondeville Jean-Philippe David Emilie Guittard Annick Maria Jean-Claude Jacques Hilary Ranson Catherine Bourgouin Chantal Dauphin-Villemant 《PloS one》2013,8(12)
In insects, the steroid hormone 20-hydroxyecdysone (20E) coordinates major developmental transitions. While the first and the final steps of 20E biosynthesis are characterized, the pathway from 7-dehydrocholesterol to 5β-ketodiol, commonly referred as the “black box”, remains hypothetical and whether there are still unidentified enzymes is unknown. The black box would include some oxidative steps, which are believed to be mediated by P450 enzymes. To identify new enzyme(s) involved in steroid synthesis, we analyzed by small-scale microarray the expression of all the genes encoding P450 enzymes of the malaria mosquito Anopheles gambiae in active steroidogenic organs of adults, ovaries from blood-fed females and male reproductive tracts, compared to inactive steroidogenic organs, ovaries from non-blood-fed females. Some genes encoding P450 enzymes were specifically overexpressed in female ovaries after a blood-meal or in male reproductive tracts but only three genes were found to be overexpressed in active steroidogenic organs of both females and males: cyp307a1, cyp4g16 and cyp6n1. Among these genes, only cyp307a1 has an expression pattern similar to other mosquito steroidogenic genes. Moreover, loss-of-function by transient RNAi targeting cyp307a1 disrupted ecdysteroid production demonstrating that this gene is required for ecdysteroid biosynthesis in Anopheles gambiae. 相似文献
107.
108.
Eliete Dalla Corte Frantz Camila Crespo-Mascarenhas Andre Rodrigues C. Barreto-Vianna Marcia Barbosa Aguila Carlos Alberto Mandarim-de-Lacerda 《PloS one》2013,8(7)
Background
The associations between obesity, hypertension and diabetes are well established, and the renin-angiotensin system (RAS) may provide a link among them. The effect of RAS inhibition on type 2 diabetes is still unclear; however, RAS seems to play an important role in the regulation of the pancreas and glucose intolerance of mice fed high-fat (HF) diet.Methods
C57BL/6 mice fed a HF diet (8 weeks) were treated with aliskiren (50 mg/kg/day), enalapril (30 mg/kg/day) or losartan (10 mg/kg/day) for 6 weeks, and the protective effects were extensively compared among groups by morphometry, stereological tools, immunostaining, Western blotting and hormonal analysis.Results
All RAS inhibitors significantly attenuated the increased blood pressure in mice fed a HF diet. Treatment with enalapril, but not aliskiren or losartan, significantly attenuated body mass (BM) gain, glucose intolerance and insulin resistance, improved the alpha and beta cell mass and prevented the reduction of plasma adiponectin. Furthermore, enalapril treatment improved the protein expression of the pancreatic islet Pdx1, GLUT2, ACE2 and Mas receptors. Losartan treatment showed the greatest AT2R expression.Conclusion
Our findings indicate that ACE inhibition with enalapril attenuated several of the deleterious effects of the HF diet. In summary, enalapril appears to be responsible for the normalization of islet morphology and function, of alpha and beta cell mass and of Pdx1 and GLUT2 expression. These protective effects of enalapril were attributed, primarily, to the reduction in body mass gain and food intake and the enhancement of the ACE2/Ang (1-7) /Mas receptor axis and adiponectin levels. 相似文献109.
Audrey Schlernitzauer Catherine Oiry Raphael Hamad Simon Galas Fabienne Cortade Béatrice Chabi Fran?ois Casas Laurence Pessemesse Gilles Fouret Christine Feillet-Coudray Gérard Cros Gérard Cabello Richard Magous Chantal Wrutniak-Cabello 《PloS one》2013,8(11)
Chicoric acid (CA) is a caffeoyl derivative previously described as having potential anti-diabetic properties. As similarities in cellular mechanism similarities between diabetes and aging have been shown, we explored on L6 myotubes the effect of CA on the modulation of intracellular pathways involved in diabetes and aging. We also determined its influence on lifespan of Caenorhabditis elegans worm (C. elegans). In L6 myotubes, CA was a potent reactive oxygen species (ROS) scavenger, reducing ROS accumulation under basal as well as oxidative stress conditions. CA also stimulated the AMP-activated kinase (AMPK) pathway and displayed various features associated with AMPK activation: CA (a) enhanced oxidative enzymatic defences through increase in glutathion peroxidase (GPx) and superoxide dismutase (SOD) activities, (b) favoured mitochondria protection against oxidative damage through up-regulation of MnSOD protein expression, (c) increased mitochondrial biogenesis as suggested by increases in complex II and citrate synthase activities, along with up-regulation of PGC-1α mRNA expression and (d) inhibited the insulin/Akt/mTOR pathway. As AMPK stimulators (e.g. the anti-diabetic agent meformin or polyphenols such as epigallocatechingallate or quercetin) were shown to extend lifespan in C. elegans, we also determined the effect of CA on the same model. A concentration-dependant lifespan extension was observed with CA (5–100 μM). These data indicate that CA is a potent antioxidant compound activating the AMPK pathway in L6 myotubes. Similarly to other AMPK stimulators, CA is able to extend C. elegans lifespan, an effect measurable even at the micromolar range. Future studies will explore CA molecular targets and give new insights about its possible effects on metabolic and aging-related diseases. 相似文献
110.