全文获取类型
收费全文 | 1554篇 |
免费 | 105篇 |
国内免费 | 3篇 |
出版年
2023年 | 7篇 |
2022年 | 12篇 |
2021年 | 20篇 |
2020年 | 13篇 |
2019年 | 10篇 |
2018年 | 20篇 |
2017年 | 24篇 |
2016年 | 37篇 |
2015年 | 65篇 |
2014年 | 61篇 |
2013年 | 82篇 |
2012年 | 96篇 |
2011年 | 116篇 |
2010年 | 70篇 |
2009年 | 57篇 |
2008年 | 91篇 |
2007年 | 73篇 |
2006年 | 71篇 |
2005年 | 72篇 |
2004年 | 58篇 |
2003年 | 85篇 |
2002年 | 84篇 |
2001年 | 9篇 |
2000年 | 8篇 |
1999年 | 18篇 |
1998年 | 24篇 |
1997年 | 17篇 |
1996年 | 17篇 |
1995年 | 16篇 |
1994年 | 18篇 |
1993年 | 15篇 |
1992年 | 10篇 |
1991年 | 11篇 |
1989年 | 15篇 |
1988年 | 15篇 |
1987年 | 8篇 |
1986年 | 11篇 |
1985年 | 8篇 |
1984年 | 10篇 |
1983年 | 10篇 |
1982年 | 9篇 |
1981年 | 16篇 |
1979年 | 8篇 |
1978年 | 9篇 |
1977年 | 7篇 |
1975年 | 9篇 |
1973年 | 7篇 |
1970年 | 7篇 |
1965年 | 8篇 |
1963年 | 6篇 |
排序方式: 共有1662条查询结果,搜索用时 15 毫秒
991.
992.
Sohi G Marchand K Revesz A Arany E Hardy DB 《Molecular endocrinology (Baltimore, Md.)》2011,25(5):785-798
Adverse events in utero, such as intrauterine growth restriction (IUGR), can permanently alter epigenetic mechanisms leading to the metabolic syndrome, which encompasses a variety of symptoms including augmented cholesterol. The major site for cholesterol homeostasis occurs via the actions of hepatic cholesterol 7α-hydroxylase (Cyp7a1), which catabolizes cholesterol to bile acids. To determine whether posttranslational histone modifications influence the long-term expression of Cyp7a1 in IUGR, we used a protein restriction model in rats. This diet during pregnancy and lactation led to IUGR offspring with decreased liver to body weight ratios, followed by increased circulating and hepatic cholesterol levels in both sexes at d 21 and exclusively in the male offspring at d 130. The augmented cholesterol was associated with decreases in the expression of Cyp7a1. Chromatin immunoprecipitation revealed that this was concomitant with diminished acetylation and enhanced methylation of histone H3 lysine 9 [K9,14], markers of chromatin silencing, surrounding the promoter region of Cyp7a1. These epigenetic modifications originate in part due to dietary-induced decreases in fetal hepatic Jmjd2a expression, a histone H3 [K9] demethylase. Collectively, these findings suggest that the augmented cholesterol observed in low-protein diet-derived offspring is due to permanent repressive posttranslational histone modifications at the promoter of Cyp7a1. Moreover, this is the first study to demonstrate that maternal undernutrition leads to long-term cholesterol dysregulation in the offspring via epigenetic mechanisms. 相似文献
993.
Arnold EM Delp SL 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2011,366(1570):1530-1539
Muscles actuate movement by generating forces. The forces generated by muscles are highly dependent on their fibre lengths, yet it is difficult to measure the lengths over which muscle fibres operate during movement. We combined experimental measurements of joint angles and muscle activation patterns during walking with a musculoskeletal model that captures the relationships between muscle fibre lengths, joint angles and muscle activations for muscles of the lower limb. We used this musculoskeletal model to produce a simulation of muscle-tendon dynamics during walking and calculated fibre operating lengths (i.e. the length of muscle fibres relative to their optimal fibre length) for 17 lower limb muscles. Our results indicate that when musculotendon compliance is low, the muscle fibre operating length is determined predominantly by the joint angles and muscle moment arms. If musculotendon compliance is high, muscle fibre operating length is more dependent on activation level and force-length-velocity effects. We found that muscles operate on multiple limbs of the force-length curve (i.e. ascending, plateau and descending limbs) during the gait cycle, but are active within a smaller portion of their total operating range. 相似文献
994.
Cadena EM Du X Gellerstedt G Li J Fillat A García-Ubasart J Vidal T Colom JF 《Bioresource technology》2011,102(4):3911-3917
Flax soda/AQ pulps were treated with different fungal laccase-mediator combinations followed by physical and chemical characterization of the pulps to obtain a thorough understanding of the laccase/mediator effects on hexenuronic acid (HexA) removal and the coupling of mediator onto pulps for fiber functionalization. Large differences were found and the presence of lauryl gallate (LG) during Trametes villosa laccase (TvL) treatment (TvL + LG) resulted in a much larger reduction of pulp-linked HexA than the combination of p-coumaric acid (PCA) and Pycnoporus cinnabarinus laccase (PcL). A major portion of LG became attached to the pulp as revealed by an increase in the kappa number and further confirmed by thioacidolysis and 1H NMR analysis of solubilized pulp fractions. Additional experiments with other chemical pulps and isolated pulp xylan and lignin revealed that HexA seems to be the sole pulp component attacked by TvL + LG. As a substrate for TvL, the reaction preference order is PCA > HexA > LG. 相似文献
995.
996.
As single agents, ABT-263 and ABT-737 (ABT), molecular antagonists of the Bcl-2 family, bind tightly to Bcl-2, Bcl-xL and Bcl-w, but not to Mcl-1, and induce apoptosis only in limited cell types. The compound 2-deoxyglucose (2DG), in contrast, partially blocks glycolysis, slowing cell growth but rarely causing cell death. Injected into an animal, 2DG accumulates predominantly in tumors but does not harm other tissues. However, when cells that were highly resistant to ABT were pre-treated with 2DG for 3 hours, ABT became a potent inducer of apoptosis, rapidly releasing cytochrome c from the mitochondria and activating caspases at submicromolar concentrations in a Bak/Bax-dependent manner. Bak is normally sequestered in complexes with Mcl-1 and Bcl-xL. 2DG primes cells by interfering with Bak-Mcl-1 association, making it easier for ABT to dissociate Bak from Bcl-xL, freeing Bak to induce apoptosis. A highly active glucose transporter and Bid, as an agent of the mitochondrial apoptotic signal amplification loop, are necessary for efficient apoptosis induction in this system. This combination treatment of cancer-bearing mice was very effective against tumor xenograft from hormone-independent highly metastasized chemo-resistant human prostate cancer cells, suggesting that the combination treatment may provide a safe and effective alternative to genotoxin-based cancer therapies. 相似文献
997.
998.
Introduction
Iodine is essential for normal fetal and neonatal development. We studied the prevalence and impact on fetal thyroid development of iodine deficiency in pregnant women in the northern part of the Paris conurbation.Materials and Methods
110 patients underwent several determinations of urinary iodine excretion (UIE) and of serum FT4, FT3, and TSH. Fetal thyroid gland size was assessed using ultrasonography.Results
We found evidence of widespread iodine deficiency (mean UIE, 49.8 µg/L [standard deviation, 2.11]). Iodine deficiency did not correlate significantly with maternal thyroid parameters but showed a significant negative correlation with fetal thyroid gland size (rho = 0.25, P = 0.02).Conclusion
Iodine deficiency during pregnancy is still a problem in our geographical area and affects the fetal thyroid gland.Clinical Trials.gov NCT00162539相似文献999.
Gómez-Marin JE de-la-Torre A Angel-Muller E Rubio J Arenas J Osorio E Nuñez L Pinzon L Mendez-Cordoba LC Bustos A de-la-Hoz I Silva P Beltran M Chacon L Marrugo M Manjarres C Baquero H Lora F Torres E Zuluaga OE Estrada M Moscote L Silva MT Rivera R Molina A Najera S Sanabria A Ramirez ML Alarcon C Restrepo N Falla A Rodriguez T Castaño G 《PLoS neglected tropical diseases》2011,5(5):e1195
Aims
To determine the incidence of congenital toxoplasmosis in Colombian newborns from 19 hospital or maternal child health services from seven different cities of five natural geographic regions (Caribbean, Central, Andean, Amazonia and Eastern).Materials and Methods
We collected 15,333 samples from umbilical cord blood between the period of March 2009 to May 2010 in 19 different hospitals and maternal-child health services from seven different cities. We applied an IgM ELISA assay (Vircell, Spain) to determine the frequency of IgM anti Toxoplasma. The results in blood cord samples were confirmed either by western blot and repeated ELISA IgM assay. In a sub-sample of 1,613 children that were negative by the anti-Toxoplasma IgM assay, the frequency of specific anti-Toxoplasma IgA by the ISAGA assay was determined. All children with positive samples by IgM, IgA, clinical diagnosis or treatment during pregnancy were recalled for confirmatory tests after day 10 of life.Results
61 positive samples for specific IgM (0.39%) and 9 positives for IgA (0.5%) were found. 143 questionnaires were positive for a clinical diagnosis or treatment for toxoplasmosis during pregnancy. 109 out of the 218 children that had some of the criteria for postnatal confirmatory tests were followed. Congenital toxoplasmosis infection was confirmed in 15 children: 7 were symptomatic, and three of them died before the first month of life (20% of lethality). A significant correlation was found between a high incidence of markers for congenital toxoplasmosis and higher mean annual rainfall for the city.Conclusions
Incidence for congenital toxoplasmosis is significantly different between hospitals or maternal child health services from different cities in Colombia. Mean annual rainfall was correlated with incidence of congenital toxoplasmosis. 相似文献1000.