全文获取类型
收费全文 | 7181篇 |
免费 | 564篇 |
国内免费 | 1篇 |
专业分类
7746篇 |
出版年
2023年 | 43篇 |
2022年 | 47篇 |
2021年 | 111篇 |
2020年 | 76篇 |
2019年 | 100篇 |
2018年 | 220篇 |
2017年 | 209篇 |
2016年 | 265篇 |
2015年 | 420篇 |
2014年 | 335篇 |
2013年 | 471篇 |
2012年 | 604篇 |
2011年 | 576篇 |
2010年 | 327篇 |
2009年 | 244篇 |
2008年 | 382篇 |
2007年 | 344篇 |
2006年 | 348篇 |
2005年 | 314篇 |
2004年 | 312篇 |
2003年 | 268篇 |
2002年 | 222篇 |
2001年 | 195篇 |
2000年 | 194篇 |
1999年 | 144篇 |
1998年 | 63篇 |
1997年 | 31篇 |
1996年 | 40篇 |
1995年 | 47篇 |
1994年 | 27篇 |
1993年 | 29篇 |
1992年 | 86篇 |
1991年 | 55篇 |
1990年 | 56篇 |
1989年 | 51篇 |
1988年 | 46篇 |
1987年 | 60篇 |
1986年 | 44篇 |
1985年 | 43篇 |
1984年 | 46篇 |
1983年 | 18篇 |
1982年 | 22篇 |
1979年 | 16篇 |
1977年 | 14篇 |
1975年 | 19篇 |
1974年 | 30篇 |
1973年 | 17篇 |
1971年 | 10篇 |
1970年 | 11篇 |
1968年 | 15篇 |
排序方式: 共有7746条查询结果,搜索用时 15 毫秒
31.
Ferreira-Gomes MS González-Lebrero RM de la Fuente MC Strehler EE Rossi RC Rossi JP 《The Journal of biological chemistry》2011,286(37):32018-32025
In this work, we set out to identify and characterize the calcium occluded intermediate(s) of the plasma membrane Ca(2+)-ATPase (PMCA) to study the mechanism of calcium transport. To this end, we developed a procedure for measuring the occlusion of Ca(2+) in microsomes containing PMCA. This involves a system for overexpression of the PMCA and the use of a rapid mixing device combined with a filtration chamber, allowing the isolation of the enzyme and quantification of retained calcium. Measurements of retained calcium as a function of the Ca(2+) concentration in steady state showed a hyperbolic dependence with an apparent dissociation constant of 12 ± 2.2 μM, which agrees with the value found through measurements of PMCA activity in the absence of calmodulin. When enzyme phosphorylation and the retained calcium were studied as a function of time in the presence of La(III) (inducing accumulation of phosphoenzyme in the E(1)P state), we obtained apparent rate constants not significantly different from each other. Quantification of EP and retained calcium in steady state yield a stoichiometry of one mole of occluded calcium per mole of phosphoenzyme. These results demonstrate for the first time that one calcium ion becomes occluded in the E(1)P-phosphorylated intermediate of the PMCA. 相似文献
32.
Kathryn A. Ayres James T. Ketchum Rogelio González-Armas Felipe Galván-Magaña Alex Hearn Fernando R. Elorriaga-Verplancken Edgar M. Hoyos-Padilla Stephen M. Kajiura 《Journal of fish biology》2021,99(5):1735-1740
Cabo Pulmo National Park was established in 1995 and has since seen a large increase in fish biomass. An unoccupied aerial vehicle (UAV) was used to survey shallow coastal habitat in which lemon sharks (Negaprion brevirostris), bull sharks (Carcharhinus leucas) and Pacific nurse sharks (Ginglymostoma unami) were recorded. Sharks were more common in the afternoon, potentially using warmer shallow areas to behaviourally thermoregulate. This study highlights UAV surveying to be a viable tool for species identification, a limitation of previous terrestrial surveys conducted in the area. 相似文献
33.
34.
Daniel R. Henríquez Felipe J. Bodaleo Carolina Montenegro-Venegas Christian González-Billault 《PloS one》2012,7(12)
Microtubule-associated protein 1B (MAP1B) is a neuronal protein involved in the stabilization of microtubules both in the axon and somatodendritic compartments. Acute, genetic inactivation of MAP1B leads to delayed axonal outgrowth, most likely due to changes in the post-translational modification of tubulin subunits, which enhances microtubule polymerization. Furthermore, MAP1B deficiency is accompanied by abnormal actin microfilament polymerization and dramatic changes in the activity of small GTPases controlling the actin cytoskeleton. In this work, we showed that MAP1B interacts with a guanine exchange factor, termed Tiam1, which specifically activates Rac1. These proteins co-segregated in neurons, and interact in both heterologous expression systems and primary neurons. We dissected the molecular domains involved in the MAP1B-Tiam1 interaction, and demonstrated that pleckstrin homology (PH) domains in Tiam1 are responsible for MAP1B binding. Interestingly, only the light chain 1 (LC1) of MAP1B was able to interact with Tiam1. Moreover, it was able to increase the activity of the small GTPase, Rac1. These results suggest that the interaction between Tiam1 and MAP1B, is produced by the binding of LC1 with PH domains in Tiam1. The formation of such a complex impacts on the activation levels of Rac1 confirming a novel function of MAP1B related with the control of small GTPases. These results also support the idea of cross-talk between cytoskeleton compartments inside neuronal cells. 相似文献
35.
Wendy González Leandro Zú?iga L. Pablo Cid Barbara Arévalo María Isabel Niemeyer Francisco V. Sepúlveda 《The Journal of biological chemistry》2013,288(8):5984-5991
Proton-gated TASK-3 K+ channel belongs to the K2P family of proteins that underlie the K+ leak setting the membrane potential in all cells. TASK-3 is under cooperative gating control by extracellular [H+]. Use of recently solved K2P structures allows us to explore the molecular mechanism of TASK-3 cooperative pH gating. Tunnel-like side portals define an extracellular ion pathway to the selectivity filter. We use a combination of molecular modeling and functional assays to show that pH-sensing histidine residues and K+ ions mutually interact electrostatically in the confines of the extracellular ion pathway. K+ ions modulate the pKa of sensing histidine side chains whose charge states in turn determine the open/closed transition of the channel pore. Cooperativity, and therefore steep dependence of TASK-3 K+ channel activity on extracellular pH, is dependent on an effect of the permeant ion on the channel pHo sensors. 相似文献
36.
Early detection of atherosclerosis is of major importance to reduce the increased incidence of cardiovascular (CV) complications observed in patients with rheumatoid arthritis (RA). Prospective studies have shown that an abnormally increased carotid intima-media thickness and the presence of plaques assessed by carotid ultrasound are good markers to predict the development of CV events in these patients. Age, classic CV risk factors, and corticosteroid use are also predictors of new plaque formation in patients with RA. Active treatment of the disease may decrease the inflammatory burden, leading to a reduction in the progression of subclinical atherosclerosis in these patients. 相似文献
37.
Julia Spencer Barthold Jobayer Hossain Alicia Olivant‐Fisher Anita Reilly T. Ernesto Figueroa Ahmad BaniHani Jennifer Hagerty Ricardo González Paul H. Noh Jeanne M. Manson 《Birth defects research. Part A, Clinical and molecular teratology》2012,94(11):900-907
BACKGROUND : Genetic and environmental factors likely influence susceptibility to nonsyndromic cryptorchidism, a common disease presenting at birth or in later childhood. We compared cases and controls to define differential risk factors for congenital versus acquired cryptorchidism. METHODS : We compared questionnaire and clinical data from cases of congenital cryptorchidism (n = 230), acquired cryptorchidism (n = 182) and hernia/hydrocele (n = 104) with a group of healthy male controls (n = 358). Potential predictor variables (p < 0.2 in univariable analysis) were included in stepwise multivariable logistic regression models. RESULTS : Temporary (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.4–0.8) or exclusive (OR, 0.6; 95% CI, 0.4–0.9) breastfeeding was reduced and soy formula feeding increased (OR, 1.8; 95% CI, 1.2–2.9) in acquired but not congenital or hernia/hydrocele groups. The highest risk estimates were observed for primary soy formula feeding with limited or no breastfeeding (OR 2.5; 95% CI, 1.4–4.3; adjusted OR, 2.7; 95% CI, 1.4–5.4) in the acquired group. Primary feeding risk estimates were equivalent or strengthened when multivariable models were limited to age greater than 2 years, full‐term or not small for gestational age, or Caucasian subjects. Pregnancy complications and increased maternal exposure to cosmetic or household chemicals were not consistently associated with either form of cryptorchidism in these models. CONCLUSIONS : Our data support reduced breastfeeding and soy formula feeding as potential risk factors for acquired cryptorchidism. Although additional studies are needed, hormonally active components of breast milk and soy formula could influence the establishment of normal testis position in the first months of life, leading to apparent ascent of testes in childhood. Birth Defects Research (Part A), 2012. © 2012 Wiley Periodicals, Inc. 相似文献
38.
María Elena González-Benito Carolina Kremer Miguel A. Ibáñez Carmen Martín 《Plant Cell, Tissue and Organ Culture》2016,127(2):359-368
The effect of antioxidants applied in one step of a cryopreservation protocol by encapsulation–dehydration on recovery and genetic stability of mint shoot tips has been studied. Glutathione (0.16 or 0.24 mM), ascorbic acid (0.28 or 0.43 mM) and α-tocopherol (vitamin E) were added to the preculture medium (0.3 M sucrose). DNA was extracted from three different types of samples: leaves from shoots, callus at the base of shoots and callus. RAPD and AFLP markers were used to assess the genetic stability. The use of antioxidants did not improve recovery after cryopreservation. One of the genotypes, ‘MEN 198’, showed higher percentage of stable samples than the other one, ‘MEN 186’ (56 vs. 37?%; considering all treatments and types of explant). The use of vitamin E improved the percentage of stable samples with respect to control treatment (no antioxidant) in ‘MEN 186’. No differences in the percentages of stable samples were observed among cryopreserved and non-cryopreserved (treated similarly without immersion in liquid nitrogen) plant material. Recovered shoots of both genotypes showed higher stability (76–80?% stable samples) than callus samples (14–22?%). 相似文献
39.
Zoraida Verde Luis Reinoso Luis Miguel Chicharro Pilar Resano Ignacio Sánchez-Hernández Jose Miguel Rodríguez González-Moro Fernando Bandrés Félix Gómez-Gallego Catalina Santiago 《PloS one》2015,10(5)
Variations in tobacco-related cancers, incidence and prevalence reflect differences in tobacco consumption in addition to genetic factors. Besides, genes related to lung cancer risk could be related to smoking behavior. Polymorphisms altering DNA repair capacity may lead to synergistic effects with tobacco carcinogen-induced lung cancer risk. Common problems in genetic association studies, such as presence of gene-by-environment (G x E) correlation in the population, may reduce the validity of these designs. The main purpose of this study was to evaluate the independence assumption for selected SNPs and smoking behaviour in a cohort of 320 healthy Spanish smokers. We found an association between the wild type alleles of XRCC3 Thr241Met or KLC3 Lys751Gln and greater smoking intensity (OR = 12.98, 95% CI = 2.86–58.82 and OR=16.90, 95% CI=2.09-142.8; respectively). Although preliminary, the results of our study provide evidence that genetic variations in DNA-repair genes may influence both smoking habits and the development of lung cancer. Population-specific G x E studies should be carried out when genetic and environmental factors interact to cause the disease. 相似文献
40.
Marcela Aida González María del Carmen Contini Nestor Millen Stella Teresita Mahieu 《Cell biochemistry and function》2012,30(8):701-708
The process of regenerating liver is the result of a balance between stimulating factors and inhibitors of hepatocyte proliferation. Melatonin and its metabolites have been found to protect tissues against oxidative damage generated by a variety of toxic agents and metabolic processes. Furthermore, studies in liver of rats showed a decrease in the liver mitochondrial hydroxylation of drugs returning to the normal state after the administration of antioxidants. This study was designed to determine, in experimental animals, whether the administration of an antioxidant agent such as melatonin could prevent cells events leading to tissue injury and hepatic dysfunction after partial hepatectomy (PH). Biliary flow (BF), oxidative stress in hepatic tissue and Na+/K+ATPase activities in whole plasma membrane were determined. PH decreased the Na+/K+ATPase activity. PH significantly reduced the BF (36%) and promoted oxidative stress with an increase of lipoperoxidation and decrease of glutathione peroxidase and catalase activities. Treatment with melatonin prevented the decrease of BF in rats with hepatectomy and normalized the Na+/K+ATPase activity. Moreover, melatonin markedly attenuated oxidative stress produced by PH. This may be the results of the higher efficacy of melatonin in scavenging various free radicals and also because of its ability in stimulating the antioxidant enzymes. We suggest that oxidative stress before and during liver regeneration has a crucial role in cholestasis, apoptotic/necrotic hepatocellular damage and the impairment in liver transport function induced by PH and that melatonin could modulate the degree of oxidative stress and through it prevent the alterations in liver function carrier. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献