全文获取类型
收费全文 | 1908篇 |
免费 | 191篇 |
专业分类
2099篇 |
出版年
2021年 | 18篇 |
2020年 | 14篇 |
2018年 | 17篇 |
2017年 | 15篇 |
2016年 | 32篇 |
2015年 | 56篇 |
2014年 | 53篇 |
2013年 | 64篇 |
2012年 | 99篇 |
2011年 | 83篇 |
2010年 | 46篇 |
2009年 | 56篇 |
2008年 | 81篇 |
2007年 | 73篇 |
2006年 | 82篇 |
2005年 | 78篇 |
2004年 | 55篇 |
2003年 | 58篇 |
2002年 | 89篇 |
2001年 | 71篇 |
2000年 | 77篇 |
1999年 | 56篇 |
1998年 | 24篇 |
1997年 | 22篇 |
1996年 | 22篇 |
1995年 | 17篇 |
1994年 | 20篇 |
1993年 | 17篇 |
1992年 | 51篇 |
1991年 | 47篇 |
1990年 | 40篇 |
1989年 | 38篇 |
1988年 | 39篇 |
1987年 | 30篇 |
1986年 | 28篇 |
1985年 | 35篇 |
1984年 | 25篇 |
1983年 | 19篇 |
1982年 | 19篇 |
1981年 | 18篇 |
1979年 | 27篇 |
1978年 | 11篇 |
1977年 | 21篇 |
1976年 | 19篇 |
1974年 | 14篇 |
1973年 | 11篇 |
1972年 | 18篇 |
1971年 | 17篇 |
1969年 | 21篇 |
1967年 | 11篇 |
排序方式: 共有2099条查询结果,搜索用时 0 毫秒
991.
The observation that muscular exercise is associated with oxidative stress in humans was first reported over 30 years ago. Since this initial report, numerous studies have confirmed that prolonged or high-intensity exercise results in oxidative damage to macromolecules in both blood and skeletal muscle. Although the primary tissue(s) responsible for reactive oxygen species (ROS) production during exercise remains a topic of debate, compelling evidence indicates that muscular activity promotes oxidant production in contracting skeletal muscle fibers. Mitochondria, NADPH oxidase, PLA2-dependent processes, and xanthine oxidase have all been postulated to contribute to contraction-induced ROS production in muscle but the primary site of contraction-induced ROS production in muscle fibers remains unclear. Nonetheless, contraction-induced ROS generation has been shown to play an important physiological function in the regulation of both muscle force production and contraction-induced adaptive responses of muscle fibers to exercise training. Although knowledge in the field of exercise and oxidative stress has grown markedly during the past 30 years, this area continues to expand and there is much more to be learned about the role of ROS as signaling molecules in skeletal muscle. 相似文献
992.
Sączewski F Kornicka A Hudson AL Laird S Scheinin M Laurila JM Rybczyńska A Boblewski K Lehmann A Gdaniec M 《Bioorganic & medicinal chemistry》2011,19(1):321-329
A series of 3-[(4,5-dihydroimidazolidin-2-yl)imino]indazoles has been synthesized as positional analogues of marsanidine, a highly selective ??2-adrenoceptor ligand. Parent compound 4a and its 4-chloro (4c) and 4-methyl (4d) derivatives display ??2-adrenoceptor affinity at nanomolar concentrations (Ki = 39.4, 15.9 and 22.6 nM, respectively) and relatively high ??2/I1 selectivity ratios of 82, 115 and 690, respectively. Evidence was obtained that these compounds act as partial agonists at ??2A-adrenoceptors. Compound 4d with intrinsic activity comparable with that of marsanidine, but lower than that of clonidine, elicited pronounced cardiovascular effects in anesthetized rats at doses as low as 0.01 mg/kg iv 相似文献
993.
Roach SL Higuchi RI Hudson AR Vassar A Grant VH Lamer R Hooper C Rungta D Syka PM Mais DE Marschke KB Zhi L 《Bioorganic & medicinal chemistry letters》2011,21(6):1658-1662
Continuing studies on tetrahydroquinoline glucocorticoid receptor anti-inflammatory agents lead to the identification of several tetrahydroquinolin-3-yl carbamates that exhibited steroid-like activity in in vitro transrepression assays with reduced transactivation of phosphoenol pyruvate carboxykinase (PEPCK), a key enzyme in the gluconeogenesis pathway. 相似文献
994.
The model species Antirrhinum majus (the garden snapdragon) has over 20 close wild relatives that are morphologically diverse and adapted to different Mediterranean environments. Hybrids between Antirrhinum species have been used successfully to identify genes underlying their phenotypic differences, and to infer how selection acts on them. To better understand the genetic basis for this diversity, we have examined the evolutionary relationships between Antirrhinum species and how these relate to geography and patterns of phenotypic variation in the genus as a whole. Large population samples and both plastid and multilocus nuclear genotypes resolved the relationships between many species and provided some support for the traditional taxonomic division of the genus into morphological subsections. Morphometric analysis of plants grown in controlled conditions supported the phenotypic distinction of the two largest subsections, and the involvement of multiple underlying genes. Incongruence between nuclear and plastid genotypes further suggested that several species have arisen after hybridization between subsections, and that some species continue to hybridize. However, all potential hybrids appear to have retained a phenotype similar to one of their ancestors, suggesting that ancestral combinations of characters are maintained by selection at many different loci. 相似文献
995.
Alan G. Hudson Pascal Vonlanthen Ole Seehausen 《Proceedings. Biological sciences / The Royal Society》2011,278(1702):58-66
The Alpine lake whitefish (Coregonus lavaretus) species complex is a classic example of a recent radiation, associated with colonization of the Alpine lakes following the glacial retreat (less than 15 kyr BP). They have formed a unique array of endemic lake flocks, each with one to six described sympatric species differing in morphology, diet and reproductive ecology. Here, we present a genomic investigation of the relationships between and within the lake flocks. Comparing the signal between over 1000 AFLP loci and mitochondrial control region sequence data, we use phylogenetic tree-based and population genetic methods to reconstruct the phylogenetic history of the group and to delineate the principal centres of genetic diversity within the radiation. We find significant cytonuclear discordance showing that the genomically monophyletic Alpine whitefish clade arose from a hybrid swarm of at least two glacial refugial lineages. Within this radiation, we find seven extant genetic clusters centred on seven lake systems. Most interestingly, we find evidence of sympatric speciation within and parallel evolution of equivalent phenotypes among these lake systems. However, we also find the genetic signature of human-mediated gene flow and diversity loss within many lakes, highlighting the fragility of recent radiations. 相似文献
996.
Hudson M 《Alternatives to laboratory animals : ATLA》2011,39(4):403-411
The 2010 Statistics of Scientific Procedures on Living Animals showed that the level of animal experimentation in Great Britain continues to rise, with just over 3.7 million procedures being conducted. This is almost exclusively due to the sustained increase in the breeding and utilisation of genetically-altered animals. Here, the general trends in the species used and the numbers and types of procedures are reviewed. In addition, the impact of the recent Government announcement to ban testing of household products on animals is discussed, along with the implications of the fish becoming the second most frequently used animal in scientific research. Finally, concerns about primate use, the REACH System, cosmetics testing and the new EU Directive on the protection of laboratory animals are explained. 相似文献
997.
Nielsen JA Chambers MA Romm E Lee LY Berndt JA Hudson LD 《Molecular and cellular biochemistry》2011,357(1-2):73-81
Cell survival proteins play an important role throughout nervous system development, normal physiological processes, and pathological conditions. Transmembrane BAX inhibitor motif 3 (TMBIM3, also known as GRINA), is a member of a family of proteins that contain a conserved BAX inhibitor-1 motif. This family of proteins includes several members that have been shown to protect cells from apoptosis. In this study, the authors show that TMBIM3 is expressed in the brain including high levels in the hippocampus. Biochemical and sequence analysis of TMBIM3 demonstrates that the rat, murine, and human genes encode an approximately 38?kDa protein with a predicted seven transmembrane domain topology. A Tmbim3 knockout mouse line did not have an obvious phenotype, but may prove useful in future studies of this family of proteins. 相似文献
998.
Guza R Kotandeniya D Murphy K Dissanayake T Lin C Giambasu GM Lad RR Wojciechowski F Amin S Sturla SJ Hudson RH York DM Jankowiak R Jones R Tretyakova NY 《Nucleic acids research》2011,39(9):3988-4006
Endogenous 5-methylcytosine ((Me)C) residues are found at all CG dinucleotides of the p53 tumor suppressor gene, including the mutational 'hotspots' for smoking induced lung cancer. (Me)C enhances the reactivity of its base paired guanine towards carcinogenic diolepoxide metabolites of polycyclic aromatic hydrocarbons (PAH) present in cigarette smoke. In the present study, the structural basis for these effects was investigated using a series of unnatural nucleoside analogs and a representative PAH diolepoxide, benzo[a]pyrene diolepoxide (BPDE). Synthetic DNA duplexes derived from a frequently mutated region of the p53 gene (5'-CCCGGCACCC GC[(15)N(3),(13)C(1)-G]TCCGCG-3', + strand) were prepared containing [(15)N(3), (13)C(1)]-guanine opposite unsubstituted cytosine, (Me)C, abasic site, or unnatural nucleobase analogs. Following BPDE treatment and hydrolysis of the modified DNA to 2'-deoxynucleosides, N(2)-BPDE-dG adducts formed at the [(15)N(3), (13)C(1)]-labeled guanine and elsewhere in the sequence were quantified by mass spectrometry. We found that C-5 alkylcytosines and related structural analogs specifically enhance the reactivity of the base paired guanine towards BPDE and modify the diastereomeric composition of N(2)-BPDE-dG adducts. Fluorescence and molecular docking studies revealed that 5-alkylcytosines and unnatural nucleobase analogs with extended aromatic systems facilitate the formation of intercalative BPDE-DNA complexes, placing BPDE in a favorable orientation for nucleophilic attack by the N(2) position of guanine. 相似文献
999.
The regulation of adenylyl cyclase activity by nitric oxide (NO) was studied in rat (Sprague-Dawley) striatal membranes. Three chemically distinct NO donors attenuated forskolin-stimulated activity but did not alter basal activity. Maximum inhibition resulted in a 50% decrease in forskolin-stimulated activity, consistent with the presence of multiple isoforms of adenylyl cyclase and our previous findings that only the forskolin-stimulated activity of the type-5 and -6 isoform family of enzymes is inhibited by NO. To monitor primarily the type-5 isoform, we examined the ability of NO donors to attenuate D(1)-agonist-stimulated adenylyl cyclase activity. Under those conditions, complete inhibition was observed. The data indicate that NO attenuates neuromodulator-stimulated cAMP signaling in the striatum. 相似文献
1000.
Nicola Ferrari Isabella M. Cattadori Javier Nespereira Annapaola Rizzoli Peter J. Hudson 《Ecology letters》2004,7(2):88-94
We investigated the role of host sex in parasite transmission and questioned: ‘Is host sex important in influencing the dynamics of infection in free living animal populations?’ We experimentally reduced the helminth community of either males or females in a yellow‐necked mice (Apodemus flavicollis) population using an anthelmintic, in replicated trapping areas, and subsequently monitored the prevalence and intensity of macroparasites in the untreated sex. We focussed on the dominant parasite Heligmosomoides polygyrus and found that reducing parasites in males caused a consistent reduction of parasitic intensity in females, estimated through faecal egg counts, but the removal of parasites in females had no significant influence on the parasites in males. This finding suggests that males are responsible for driving the parasite infection in the host population and females may play a relatively trivial role. The possible mechanisms promoting such patterns are discussed. 相似文献