全文获取类型
收费全文 | 3862篇 |
免费 | 239篇 |
国内免费 | 1篇 |
出版年
2024年 | 3篇 |
2023年 | 27篇 |
2022年 | 32篇 |
2021年 | 113篇 |
2020年 | 74篇 |
2019年 | 109篇 |
2018年 | 136篇 |
2017年 | 124篇 |
2016年 | 168篇 |
2015年 | 246篇 |
2014年 | 230篇 |
2013年 | 285篇 |
2012年 | 325篇 |
2011年 | 288篇 |
2010年 | 190篇 |
2009年 | 196篇 |
2008年 | 243篇 |
2007年 | 221篇 |
2006年 | 182篇 |
2005年 | 176篇 |
2004年 | 153篇 |
2003年 | 129篇 |
2002年 | 108篇 |
2001年 | 53篇 |
2000年 | 32篇 |
1999年 | 40篇 |
1998年 | 26篇 |
1997年 | 14篇 |
1996年 | 18篇 |
1995年 | 11篇 |
1994年 | 15篇 |
1993年 | 9篇 |
1992年 | 13篇 |
1991年 | 10篇 |
1990年 | 9篇 |
1989年 | 14篇 |
1988年 | 8篇 |
1987年 | 6篇 |
1986年 | 5篇 |
1985年 | 8篇 |
1984年 | 7篇 |
1983年 | 5篇 |
1982年 | 5篇 |
1981年 | 5篇 |
1979年 | 7篇 |
1978年 | 3篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 3篇 |
排序方式: 共有4102条查询结果,搜索用时 15 毫秒
991.
Santos LL Magalhães Mde C Januário JN Aguiar MJ Carvalho MR 《Genetics and molecular research : GMR》2006,5(1):33-44
Phenylketonuria (PKU) is one of the few genetic diseases in which mental retardation can be prevented. Hence, diagnosis and treatment must be established early. PKU treatment consists of a phenylalanine-restricted diet supplemented with a phenylalanine-free mixture of amino acids. However, it is difficult to adhere to this diet. In the last decade, a better comprehension of the biochemistry, genetics and molecular basis of the disease, as well as the need for easier treatment, led to the development of several new therapeutic strategies for PKU. In the present study, we evaluated these new therapeutic options in terms of theoretical basis, methodologies, efficacy, and costs. 相似文献
992.
Bovine fetal fibroblast cells were treated with ethidium bromide at a low concentration for 15 passages in culture to determine its effect on mitochondrial DNA copy number and on cell metabolism. Mitochondrial membrane potential and lactate production were estimated in order to characterize cell metabolism. In addition, mitochondrial DNA ND5 in proportion to a nuclear gene (luteinizing hormone receptor) was determined at the 1st, 2nd, 3rd, 10th, and 15th passages using semi-quantitative PCR amplification. Treated cells showed a lower mitochondrial membrane potential and higher levels of lactate production compared with control cells. However, the mitochondrial DNA/nuclear DNA ratio was higher in treated cells compared with control cells at the 10th and 15th passages. This ratio changed between the 3rd and 10th passages. Despite a clear impairment in mitochondrial function, ethidium bromide treatment did not lead to mitochondrial DNA depletion. It is possible that in response to a lower synthesis of ATP, due to an impairment in oxidative phosphorylation, treated cells develop a mechanism to resist the ethidium bromide effect on mtDNA replication, resulting in an increase in mitochondrial DNA copy number. 相似文献
993.
Nery FC Bressan GC Alborghetti MR Passos DO Kuniyoshi TM Ramos CH Oyama S Kobarg J 《Biological chemistry》2006,387(5):577-582
Ki-1/57 is a 57-kDa cytoplasmic and nuclear protein associated with protein kinase activity and is hyper-phosphorylated on Ser/Thr residues upon cellular activation. In previous studies we identified the receptor of activated kinase-1 (RACK1), a signaling adaptor protein that binds activated PKC, as a protein that interacts with Ki-1/57. Here we demonstrate that the far-UV circular dichroism spectrum of the WD repeat-containing RACK1 protein shows an unusual positive ellipticity at 229 nm, which in other proteins of the WD family has been attributed to surface tryptophans that are quenchable by N-bromosuccinimide (NBS). As well as NBS, in vitro binding of 6xHis-Ki-1/57(122-413) and 6xHis-Ki-1/57(264-413) can also quench the positive ellipticity of the RACK1 spectrum. We generated a model of RACK1 by homology modeling using a G protein beta subunit as template. Our model suggests the family-typical seven-bladed beta-propeller, with an aromatic cluster around the central tunnel that contains four Trp residues (17, 83, 150, 170), which are likely involved in the interaction with Ki-1/57. 相似文献
994.
Pre-tensed and conventional starts that exert, respectively, large and small forces against the starting blocks in the "set" position (0.186 vs. 0.113 N per newton of body weight) were analyzed. The starts were videotaped, and the horizontal forces exerted on feet and hands were obtained from separate force plates. In the pre-tensed start, the legs received larger forward impulses early in the acceleration (0.18 vs. 0.15 N x s per kilogram of mass in the first 0.05 s), but the hands received larger backward impulses (-0.08 vs. -0.04 N x s x kg(-1)). At the end of the acceleration phase, there was no significant difference in horizontal velocity between the two types of start and only trivial differences in the center of mass positions. The results did not show a clear performance change when the feet were pressed hard against the blocks while waiting for the gun. 相似文献
995.
Dias MV Canduri F da Silveira NJ Czekster CM Basso LA Palma MS Santos DS de Azevedo WF 《Cell biochemistry and biophysics》2006,44(3):375-384
The development of new therapies against infectious diseases is vital in developing countries. Among infectious diseases, tuberculosis is considered the leading cause of death. A target for development of new drugs is the tryptophan pathway. The last enzyme of this pathway, tryptophan synthase (TRPS), is responsible for conversion of the indole 3-glycerol phosphate into indol and the condensation of this molecule with serine-producing tryptophan. The present work describes the molecular models of TRPS from Mycobacterium tuberculosis (MtTRPS) complexed with six inhibitors, the indole 3-propanol phosphate and five arylthioalkyl-phosphonated analogs of substrate of the alpha-subunit. The molecular models of MtTRPS present good stereochemistry, and the binding of the inhibitors is favorable. Thus, the generated models can be used in the design of more specific drugs against tuberculosis and other infectious diseases. 相似文献
996.
Rádis-Baptista G Moreno FB de Lima Nogueira L Martins AM de Oliveira Toyama D Toyama MH Cavada BS de Azevedo WF Yamane T 《Cell biochemistry and biophysics》2006,44(3):412-423
Snake venom (sv) C-type lectins encompass a group of hemorrhagic toxins that are capable of interfering with blood stasis.
A very well-studied svC-type lectin is the heterodimeric toxin, convulxin (CVX), from the venom of South American rattlesnake
Crotalus durissus terrificus. CVX is able to activate platelets and induce their aggregation by acting via p62/GPVI collagen receptor. By using polymerase
chain reaction homology screening, we have cloned several cDNA precursors of CVX subunit homologs. One of them, named crotacetin
(CTC) β-subunit, predicts a polypeptide with a topology very similar to the tridimensional conformations of other subunits of
CVX-like snake toxins, as determined by computational analysis. Using gel permeation and reverse-phase high-performance liquid
chromatography, CTC was purified from C. durissus venoms. CTC can be isolated from the venom of several C. durissus subspecies, but its quantitative predominance is in the venom of C. durissus cascavella. Functional analysis indicates that CTC induces platelet aggregation, and, importantly, exhibits an antimicrobial activity
against Gram-positive and-negative bacteria, comparable with CVX. 相似文献
997.
de Menezes GC Tavares-Dias M Ono EA de Andrade JI Brasil EM Roubach R Urbinati EC Marcon JL Affonso EG 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2006,145(2):274-279
This study evaluated the efficacy of dietary vitamin C (ascorbic acid or AA), vitamin E (alpha-tocopherol or alpha-T), and C+E supplementation on the blood parameters of Arapaima gigas grown in net cages for 45 days. Four treatments were tested: control (commercial feed); C800; E500 and C+E (800+500) with supplementation of 800 mg AA kg(-1), 500 mg alpha-T kg(-1) and 800+500 mg AA+alpha-T kg(-1), respectively. Hematocrit (Ht), red blood cells (RBC), and hemoglobin concentration (Hb) (oxidative status indicators), thrombocytes and leukocytes (immunological indicators), plasma protein and glucose were evaluated. Fish fed vitamin C and C+E supplemented diets showed greater weight gain and survival. Dietary vitamin C and C+E diet supplementation resulted in increased Ht, Hb, RBC, MCHC, total leukocytes, total proteins, thrombocytes and eosinophils compared to the control and alpha-T. The alpha-tocopherol-supplemented diet reduced the number of total thrombocytes, lymphocytes and neutrophils and increased glucose and eosinophils relatively to the control. In general, leukocytes and thrombocytes were good indicators of the efficiency of vitamin on the defense mechanism of the A. gigas reared in cages. Results indicate that high alpha-T diet supplementation provides no benefit for the maintenance of the oxidative or the immunological status of A. gigas. However, it was demonstrated that high dietary AA improves A. gigas immunological status. Red blood cell indices and immune system indicators showed no synergistic effect between the vitamins after supplementing the A. gigas diet with alpha-T+AA. 相似文献
998.
999.
Carine Aubry A. James Wilson Daniel Emmerson Emma Murphy Yu Yam Chan Michael P. Dickens Marcos D. García Paul R. Jenkins Sachin Mahale Bhabatosh Chaudhuri 《Bioorganic & medicinal chemistry》2009,17(16):6073-6084
We present the design, synthesis and biological activity of a new series of substituted 3-(2-(1H-indol-1-yl)ethyl)-1H-indoles and 1,2-di(1H-indol-1-yl)alkanes as selective inhibitors of CDK4/cyclin D1. The compounds were designed to explore the relationship between the connection mode of the indolyl moieties and their CDK inhibitory activities. We found all the above-mentioned designed compounds to be selective inhibitors of CDK4/cyclin D1 compared to the closely related CDK2/cyclin A, with IC50 for the best compounds 10m and 13a being 39 and 37 μm, respectively. 相似文献
1000.
Sidinei Magela Thomaz Priscilla Carvalho Roger Paulo Mormul Fernando Alves Ferreira Márcio José Silveira Thaísa Sala Michelan 《Acta Oecologica》2009,35(5):614-620
Two exotic invasive macrophyte species (the emergent Urochloa subquadripara - tenner-grass - and the submersed Hydrilla verticillata - hydrilla) were investigated in a large sub-tropical reservoir. We analyzed their occurrences over an extended period and tested the hypothesis that macrophyte richness decreases their invasibility. The alternative hypothesis that the occurrence of these exotics is affected by fetch and underwater radiation (important determinants of macrophyte assemblage composition in this reservoir) was also tested. Incidence data (presence/absence) was obtained over 9.5 years at 235 stations. Logistic regression was applied to test whether the likelihood of occurrence of these two species was affected by macrophyte richness, fetch or underwater radiation. Tenner-grass was recorded at a high frequency and quickly recovered from disturbances caused by water drawdown. In contrast, H. verticillata was first recorded in 3 sites in January 2007, but it spread quickly, reaching 30.5% of the sites 19 months later. The main channel of the Paraná River was the main source of propagules for this species. The likelihood of occurrence of tenner-grass was positively affected by macrophyte richness but negatively affected by fetch. Thus, wave disturbance is probably more important than diversity in preventing invasion by this species. Hydrilla, by contrast, was negatively affected by macrophyte richness and positively affected by fetch and underwater radiation. Although this result might indicate that macrophyte diversity prevents hydrilla invasion, this is probably not true because hydrilla colonized deeper sites where few species of plant exist. Resistance to disturbances caused by water drawdown (tenner-grass) and waves (hydrilla) as well as persistency of tenner-grass and fast spread of hydrilla make these exotic species a cause for concern because of their potential impacts on water uses and maintenance of diversity. 相似文献