全文获取类型
收费全文 | 4338篇 |
免费 | 354篇 |
专业分类
4692篇 |
出版年
2022年 | 36篇 |
2021年 | 61篇 |
2020年 | 44篇 |
2019年 | 39篇 |
2018年 | 67篇 |
2017年 | 54篇 |
2016年 | 109篇 |
2015年 | 157篇 |
2014年 | 174篇 |
2013年 | 256篇 |
2012年 | 327篇 |
2011年 | 344篇 |
2010年 | 204篇 |
2009年 | 202篇 |
2008年 | 284篇 |
2007年 | 276篇 |
2006年 | 275篇 |
2005年 | 243篇 |
2004年 | 234篇 |
2003年 | 243篇 |
2002年 | 244篇 |
2001年 | 40篇 |
2000年 | 35篇 |
1999年 | 44篇 |
1998年 | 62篇 |
1997年 | 40篇 |
1996年 | 39篇 |
1995年 | 37篇 |
1994年 | 35篇 |
1993年 | 28篇 |
1992年 | 25篇 |
1991年 | 20篇 |
1990年 | 28篇 |
1989年 | 18篇 |
1988年 | 14篇 |
1987年 | 16篇 |
1985年 | 18篇 |
1984年 | 18篇 |
1983年 | 17篇 |
1982年 | 17篇 |
1981年 | 17篇 |
1980年 | 11篇 |
1979年 | 16篇 |
1978年 | 13篇 |
1977年 | 13篇 |
1976年 | 17篇 |
1975年 | 12篇 |
1974年 | 16篇 |
1972年 | 13篇 |
1969年 | 9篇 |
排序方式: 共有4692条查询结果,搜索用时 15 毫秒
141.
Céline Boileau Richard Auria Sylvain Davidson Laurence Casalot Pierre Christen Pierre-Pol Liebgott Yannick Combet-Blanc 《Biotechnology for biofuels》2016,9(1):269
Background
Thermotoga maritima and T. neapolitana are hyperthermophile bacteria chosen by many research teams to produce bio-hydrogen because of their potential to ferment a wide variety of sugars with the highest theoretical H2/glucose yields. However, to develop economically sustainable bio-processes, the culture medium formulation remained to be optimized. The main aim of this study was to quantify accurately and specifically the effect of thiosulfate, used as sulfured nutriment model, on T. maritima growth, yields and productivities of hydrogen. The results were obtained from batch cultures, performed into a bioreactor, carefully controlled, and specifically designed to prevent the back-inhibition by hydrogen.Results
Among sulfured nutriments tested, thiosulfate, cysteine, and sulfide were found to be the most efficient to stimulate T. maritima growth and hydrogen production. In particular, under our experimental conditions (glucose 60 mmol L?1 and yeast extract 1 g L?1), the cellular growth was limited by thiosulfate concentrations lower than 0.06 mmol L?1. Under these conditions, the cellular yield on thiosulfate (Y X/Thio) could be determined at 3617 mg mmol?1. In addition, it has been shown that the limitations of T. maritima growth by thiosulfate lead to metabolic stress marked by a significant metabolic shift of glucose towards the production of extracellular polysaccharides (EPS). Finally, it has been estimated that the presence of thiosulfate in the T. maritima culture medium significantly increased the cellular and hydrogen productivities by a factor 6 without detectable sulfide production.Conclusions
The stimulant effects of thiosulfate at very low concentrations on T. maritima growth have forced us to reconsider its role in this species and more probably also in all thiosulfato-reducer hyperthermophiles. Henceforth, thiosulfate should be considered in T. maritima as (1) an essential sulfur source for cellular materials when it is present at low concentrations (about 0.3 mmol g?1 of cells), and (2) as both sulfur source and detoxifying agent for H2 when thiosulfate is present at higher concentrations and, when, simultaneously, the pH2 is high. Finally, to improve the hydrogen production in bio-processes using Thermotoga species, it should be recommended to incorporate thiosulfate in the culture medium.142.
143.
Axel Van Der Gucht Ouidad Zehou Soraya Djelbani-Ahmed Laurence Valeyrie-Allanore Nicolas Ortonne Pierre Brugières Pierre Wolkenstein Alain Luciani Alain Rahmouni Emilie Sbidian Emmanuel Itti 《PloS one》2016,11(3)
Background
To investigate the diagnostic and prognostic performances of 18F-FDG PET/CT measures of metabolic tumour burden in patients with neurofibromatosis type-1 (NF1), suspect of malignant transformation.Methods
This retrospective study included 49 patients (15–60 years old, 30 women) with a diagnosis of NF1, followed in our Reference Centre for Rare Neuromuscular Diseases, who presented clinical signs of tumour progression (pain, neurological deficit, tumour growth). Quantitative metabolic parameters were measured on 149 tumoral targets, using semi-automatic software and the best cut off values to predict transformation was assessed by Receiver Operating Characteristics (ROC) analysis. Prognostic value of PET/CT metabolic parameters was assessed by Kaplan-Meier estimates of overall survival.Results
Lesions were histologically documented in 40 patients: a sarcomatous transformation was found in 16, a dysplastic neurofibroma (NF) in 7, and a benign NF in 17; in the remaining 9 patients, a minimal follow-up of 12 mo (median 59 mo) confirmed the absence of transformation. The optimal cut off values for detection of malignant transformation were, in decreasing order of area under the ROC curves, a tumour-to-liver (T/L) ratio >2.5, SUVmax > 4.5, total lesion glycolysis (TLG) > 377, total metabolic tumour volume (TMTV) > 88 cm3, and heterogeneity index (HIsuv) > 1.69. The best prognostic marker was the TLG: the 4-y estimates of survival were 97% [95% CI, 90% - 100%] in patients with TLG ≤ 377 vs. 27% [95% CI, 5% - 49%] in patients with TLG > 377 (P < 0.0001; χ2 27.85; hazard ratio 13.27 [95% CI, 3.72–47.35]). T/L ratio, SUVmax and TMTV demonstrated slightly lower performance to predict survival, with χ2 ranging 14.41–19.12. The HIsuv index was not predictive of survival.Conclusion
Our study demonstrates that TLG and TMTV, as PET/CT measures of metabolic tumour burden, may be used clinically to identify sarcomatous transformation in patients with NF1 and predict overall survival, with a higher specificity for the TLG. Conventional measures such as the SUVmax, and T/L ratio also demonstrate high prognostic value. 相似文献144.
Julia A. Sabet Lara K. Park Lakshmanan K. Iyer Albert K. Tai Gar Yee Koh Anna C. Pfalzer Laurence D. Parnell Joel B. Mason Zhenhua Liu Alexander J. Byun Jimmy W. Crott 《PloS one》2016,11(3)
Background
The importance of maternal nutrition to offspring health and risk of disease is well established. Emerging evidence suggests paternal diet may affect offspring health as well.Objective
In the current study we sought to determine whether modulating pre-conception paternal B vitamin intake alters intestinal tumor formation in offspring. Additionally, we sought to identify potential mechanisms for the observed weight differential among offspring by profiling hepatic gene expression and lipid content.Methods
Male Apc1638N mice (prone to intestinal tumor formation) were fed diets containing replete (control, CTRL), mildly deficient (DEF), or supplemental (SUPP) quantities of vitamins B2, B6, B12, and folate for 8 weeks before mating with control-fed wild type females. Wild type offspring were euthanized at weaning and hepatic gene expression profiled. Apc1638N offspring were fed a replete diet and euthanized at 28 weeks of age to assess tumor burden.Results
No differences in intestinal tumor incidence or burden were found between male Apc1638N offspring of different paternal diet groups. Although in female Apc1638N offspring there were no differences in tumor incidence or multiplicity, a stepwise increase in tumor volume with increasing paternal B vitamin intake was observed. Interestingly, female offspring of SUPP and DEF fathers had a significantly lower body weight than those of CTRL fed fathers. Moreover, hepatic trigylcerides and cholesterol were elevated 3-fold in adult female offspring of SUPP fathers. Weanling offspring of the same fathers displayed altered expression of several key lipid-metabolism genes. Hundreds of differentially methylated regions were identified in the paternal sperm in response to DEF and SUPP diets. Aside from a few genes including Igf2, there was a striking lack of overlap between these genes differentially methylated in sperm and differentially expressed in offspring.Conclusions
In this animal model, modulation of paternal B vitamin intake prior to mating alters offspring weight gain, lipid metabolism and tumor growth in a sex-specific fashion. These results highlight the need to better define how paternal nutrition affects the health of offspring. 相似文献145.
Stefanie M. Hixson Kruti Shukla Lesley G. Campbell Rebecca H. Hallett Sandy M. Smith Laurence Packer Michael T. Arts 《PloS one》2016,11(3)
Nutritional enhancement of crops using genetic engineering can potentially affect herbivorous pests. Recently, oilseed crops have been genetically engineered to produce the long-chain omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at levels similar to that found in fish oil; to provide a more sustainable source of these compounds than is currently available from wild fish capture. We examined some of the growth and development impacts of adding EPA and DHA to an artificial diet of Pieris rapae, a common pest of Brassicaceae plants. We replaced 1% canola oil with EPA: DHA (11:7 ratio) in larval diets, and examined morphological traits and growth of larvae and ensuing adults across 5 dietary treatments. Diets containing increasing amounts of EPA and DHA did not affect developmental phenology, larval or pupal weight, food consumption, nor larval mortality. However, the addition of EPA and DHA in larval diets resulted in progressively heavier adults (F 4, 108 = 6.78; p = 0.011), with smaller wings (p < 0.05) and a higher frequency of wing deformities (R = 0.988; p = 0.001). We conclude that the presence of EPA and DHA in diets of larval P. rapae may alter adult mass and wing morphology; therefore, further research on the environmental impacts of EPA and DHA production on terrestrial biota is advisable. 相似文献
146.
147.
148.
Yicong Ma Sajal?K. Ghosh David?A. DiLena Sambhunath Bera Laurence?B. Lurio Atul?N. Parikh Sunil?K. Sinha 《Biophysical journal》2016,110(6):1355-1366
The cholesterol partitioning and condensing effect in the liquid-ordered (Lo) and liquid-disordered (Ld) phases were systematically investigated for ternary mixture lipid multilayers consisting of 1:1 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/1,2-dioleoyl-sn-glycero-3-phosphocholine with varying concentrations of cholesterol. X-ray lamellar diffraction was used to deduce the electron density profiles of each phase. The cholesterol concentration in each phase was quantified by fitting of the electron density profiles with a newly invented basic lipid profile scaling method that minimizes the number of fitting parameters. The obtained cholesterol concentration in each phase versus total cholesterol concentration in the sample increases linearly for both phases. The condensing effect of cholesterol in ternary lipid mixtures was evaluated in terms of phosphate-to-phosphate distances, which together with the estimated cholesterol concentration in each phase was converted into an average area per molecule. In addition, the cholesterol position was determined to a precision of (±0.7Å) and an increase of disorder in the lipid packing in the Lo phase was observed for total cholesterol concentration of 20∼30%. 相似文献
149.
150.
Loic Verlingue Aurélien Dugourd Gautier Stoll Emmanuel Barillot Laurence Calzone Arturo Londoño‐Vallejo 《Aging cell》2016,15(6):1018-1026
Altered molecular responses to insulin and growth factors (GF) are responsible for late‐life shortening diseases such as type‐2 diabetes mellitus (T2DM) and cancers. We have built a network of the signaling pathways that control S‐phase entry and a specific type of senescence called geroconversion. We have translated this network into a Boolean model to study possible cell phenotype outcomes under diverse molecular signaling conditions. In the context of insulin resistance, the model was able to reproduce the variations of the senescence level observed in tissues related to T2DM's main morbidity and mortality. Furthermore, by calibrating the pharmacodynamics of mTOR inhibitors, we have been able to reproduce the dose‐dependent effect of rapamycin on liver degeneration and lifespan expansion in wild‐type and HER2–neu mice. Using the model, we have finally performed an in silico prospective screen of the risk–benefit ratio of rapamycin dosage for healthy lifespan expansion strategies. We present here a comprehensive prognostic and predictive systems biology tool for human aging. 相似文献