全文获取类型
收费全文 | 660篇 |
免费 | 27篇 |
专业分类
687篇 |
出版年
2022年 | 3篇 |
2021年 | 6篇 |
2020年 | 3篇 |
2017年 | 7篇 |
2016年 | 11篇 |
2015年 | 19篇 |
2014年 | 26篇 |
2013年 | 19篇 |
2012年 | 42篇 |
2011年 | 33篇 |
2010年 | 15篇 |
2009年 | 16篇 |
2008年 | 24篇 |
2007年 | 33篇 |
2006年 | 25篇 |
2005年 | 35篇 |
2004年 | 46篇 |
2003年 | 20篇 |
2002年 | 23篇 |
2001年 | 23篇 |
2000年 | 20篇 |
1999年 | 10篇 |
1998年 | 11篇 |
1997年 | 7篇 |
1996年 | 5篇 |
1995年 | 10篇 |
1994年 | 8篇 |
1992年 | 11篇 |
1991年 | 15篇 |
1990年 | 17篇 |
1989年 | 11篇 |
1988年 | 15篇 |
1987年 | 15篇 |
1986年 | 13篇 |
1985年 | 15篇 |
1984年 | 7篇 |
1983年 | 6篇 |
1982年 | 5篇 |
1981年 | 9篇 |
1980年 | 4篇 |
1979年 | 5篇 |
1977年 | 3篇 |
1976年 | 5篇 |
1975年 | 6篇 |
1974年 | 2篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1971年 | 2篇 |
1968年 | 2篇 |
1966年 | 4篇 |
排序方式: 共有687条查询结果,搜索用时 15 毫秒
61.
Chung JU Kim SY Lim JO Choi HK Kang SU Yoon HS Ryu H Kang DW Lee J Kang B Choi S Toth A Pearce LV Pavlyukovets VA Lundberg DJ Blumberg PM 《Bioorganic & medicinal chemistry》2007,15(18):6043-6053
A series of alpha-substituted N-(4-tert-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea analogues have been investigated as TRPV1 receptor antagonists. alpha-Methyl substituted analogues showed potent and stereospecific antagonism to the action of capsaicin on rat TRPV1 heterologously expressed in Chinese hamster ovary cells. In particular, compounds 14 and 18, which possess the R-configuration, exhibited excellent potencies (respectively, K(i)=41 and 39.2 nM and K(i(ant))=4.5 and 37 nM). 相似文献
62.
Corrigendum to Wagner et al.: Natural soil microbes alter flowering phenology and the intensity of selection on flowering time in a wild Arabidopsis relative 下载免费PDF全文
63.
Mats Sjöling Kristina Lundberg Erling Englund Anton Westman Miek C Jong 《BMC research notes》2011,4(1):1-7
Background
Depression and anxiety disorders have a high disease burden and as many as 15% of young people report mental health problems. Binge drinking, which is a particularly harmful way of consuming alcohol, is common among secondary school students. The aim of this study was to examine the association between binge drinking and self-reported mental health in boys and girls aged 12 to 18 years.Findings
This cross-sectional analysis was performed on data collected by the Community Health Service (GGD) Brabant Zuidoost, the Netherlands, in 2007. In this Youth Survey, 10 090 randomly selected adolescents aged 12 tot 18 years were each sent a letter, a questionnaire, and a user name and log-in code for if they preferred to complete the Internet version of the questionnaire. Mental health was assessed using the Mental Health Inventory (MHI-5), a short 5-item questionnaire to detect feelings of depression and anxiety. Participants were asked about current alcohol consumption, their relationship with their parents, drug use, and sociodemographic data. Corrected for confounders, binge drinking and mental health problems were associated in the 12 to 15 year old girls (OR 2.43; 95% CI 1.86-3.17, p = 0.000) and boys (OR 1.64, 95% CI 1.19-2.27, p = 0.003). The majority of the 16 to 18 year old adolescents had been binge drinking in the previous 4 weeks (69.6% boys and 56.8% girls). In this age group, boys with mental health problems were less likely to be classified as binge drinkers than were boys without mental health problems (OR 0.63, 95% CI 0.45-0.87, p = 0.005). No such association between binge drinking and mental health was found in girls of this age.Conclusion
Girls and boys aged 12-15 years were classified as binge drinkers significantly more often when they reported poor mental health. Because binge drinking damages the brain, especially at a young age, it is important that health professionals are alert to possible binge drinking when young adolescents report mental health problems and should ask their patients about their drinking behaviour. Likewise, if youngsters under 16 present with binge drinking, they should be asked whether they are anxious or depressed. 相似文献64.
Otoconia are bio-crystals anchored to the macular sensory epithelium of the utricle and saccule in the inner ear for motion sensing and bodily balance. Otoconia dislocation, degeneration and ectopic calcification can have detrimental effects on balance and vertigo/dizziness, yet the mechanism underlying otoconia formation is not fully understood. In this study, we show that selected matrix components are recruited to form the crystal matrix and sequester Ca(2+) for spatial specific formation of otoconia. Specifically, otoconin-90 (Oc90) binds otolin through both domains (TH and C1q) of otolin, but full-length otolin shows the strongest interaction. These proteins have much higher expression levels in the utricle and saccule than other inner ear epithelial tissues in mice. In vivo, the presence of Oc90 in wildtype (wt) mice leads to an enrichment of Ca(2+) in the luminal matrices of the utricle and saccule, whereas absence of Oc90 in the null mice leads to drastically reduced matrix-Ca(2+). In vitro, either Oc90 or otolin can increase the propensity of extracellular matrix to calcify in cell culture, and co-expression has a synergistic effect on calcification. Molecular modeling and sequence analysis predict structural features that may underlie the interaction and Ca(2+)-sequestering ability of these proteins. Together, the data provide a mechanism for the otoconial matrix assembly and the role of this matrix in accumulating micro-environmental Ca(2+) for efficient CaCO(3) crystallization, thus uncover a critical process governing spatial specific otoconia formation. 相似文献
65.
66.
Organophosphorus compounds (OPs) interfere with the catalytic mechanism of acetylcholinesterase (AChE) by rapidly phosphorylating the catalytic serine residue. The inhibited enzyme can at least partly be reactivated with nucleophilic reactivators such as oximes. The covalently attached OP conjugate may undergo further intramolecular dealkylation or deamidation reactions, a process termed "aging" that results in an enzyme considered completely resistant to reactivation. Of particular interest is the inhibition and aging reaction of the OP compound tabun since tabun conjugates display an extraordinary resistance toward most reactivators of today. To investigate the structural basis for this resistance, we determined the crystal structures of Mus musculus AChE (mAChE) inhibited by tabun prior to and after the aging reaction. The nonaged tabun conjugate induces a structural change of the side chain of His447 that uncouples the catalytic triad and positions the imidazole ring of His447 in a conformation where it may form a hydrogen bond to a water molecule. Moreover, an unexpected displacement of the side chain of Phe338 narrows the active site gorge. In the crystal structure of the aged tabun conjugate, the side chains of His447 and Phe338 are reversed to the conformation found in the apo structure of mAChE. A hydrogen bond between the imidazole ring of His447 and the ethoxy oxygen of the aged tabun conjugate stabilizes the side chain of His447. The displacement of the side chain of Phe338 into the active site gorge of the nonaged tabun conjugate may interfere with the accessibility of reactivators and thereby contribute to the high resistance of tabun conjugates toward reactivation. 相似文献
67.
Perturbation of DNA hairpins containing the EcoRI recognition site by hairpin loops of varying size and composition: physical (NMR and UV) and enzymatic (EcoRI) studies. 总被引:1,自引:2,他引:1 下载免费PDF全文
M W Germann B W Kalisch P Lundberg H J Vogel J H van de Sande 《Nucleic acids research》1990,18(6):1489-1498
We have investigated loop-induced structural perturbation of the stem structure in hairpins d(GAATTCXnGAATTC) (X = A, T and n = 3, 4, 5 and 6) that contain an EcoRI restriction site in close proximity to the hairpin loop. Oligonucleotides containing either a T3 or a A3 loop were not hydrolyzed by the restriction enzyme and also showed only weak binding to EcoRI in the absence of the cofactor Mg2+. In contrast, hairpins with larger loops are hydrolyzed by the enzyme at the scission site next to the loop although the substrate with a A4 loop is significantly more resistant than the oligonucleotide containing a T4 loop. The hairpin structures with 3 loop residues were found to be thermally most stable while larger hairpin loops resulted in structures with lower melting temperatures. The T-loop hairpins are thermally more stable than the hairpins containing the same number of A residues in the loop. As judged from proton NMR spectroscopy and the thermodynamic data, the base pair closest to the hairpin loop did form in all cases studied. The hairpin loops did, however, affect the conformation of the stem structure of the hairpins. From 31P and 1H NMR spectroscopy we conclude that the perturbation of the stem structure is stronger for smaller hairpin loops and that the extent of the perturbation is limited to 2-3 base pairs for hairpins with T3 or A4 loops. Our results demonstrate that hairpin loops modulate the conformation of the stem residues close to the loop and that this in turn reduces the substrate activity for DNA sequence specific proteins. 相似文献
68.
Uncertain biotic and abiotic interactions in benthic communities 总被引:1,自引:0,他引:1
We analyze marine benthic communities at different sites in Skagerrak with the purpose of understanding the role of exogenous and endogenous factors in explaining the species' temporal dynamics. The previous finding that the dynamics of these species communities are mainly driven and synchronized by environmental (temperature) forcing was only weakly supported when analyzing single-species dynamics at five sites where four of the species were present every year. There was no consistent pattern in how the temperature affected the realized per capita growth rate, either across species at a given site, or among sites for a given species. Furthermore, there was no net-interaction from the community on a given species strong enough to give rise to second-order dynamics. However, when implementing a Multi Dimensional Scaling (MDS) analysis and incorporating all sampling sites and species -we found that the different communities clustered in relation to depth, hence, communities at the same depth were more "similar" than communities at different depth. Revealing the underlying interactions shaping these marine benthic communities is a challenge that calls for an array of various and complementary approaches. 相似文献
69.
70.