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81.
Szekely J Wang H Peplowski KM Knutson CG Marnett LJ Rizzo CJ 《Nucleosides, nucleotides & nucleic acids》2008,27(2):103-109
Short, "one-pot" syntheses of malondialdehyde adducts of deoxyguanosine, deoxyadenosine, and deoxycytidine are described. These syntheses proceed in improved yield and easier purification than previous syntheses and are well suited for the preparation of isotopically labeled nucleoside adducts for biomarker and metabolic studies. 相似文献
82.
Kovacs K Hanto K Bognar Z Tapodi A Bognar E Kiss GN Szabo A Rappai G Kiss T Sumegi B Gallyas F 《Molecular and cellular biochemistry》2009,321(1-2):155-164
We studied cardioprotective as well as Akt and extracellular signal-activated kinase (ERK) activating effect of a Ca(2+) antagonist and a beta-adrenergic receptor blocker during ischemia-reperfusion, and compared these properties of the substances with that of a poly(ADP-ribose) polymerase (PARP) inhibitor used as a positive control throughout the experiments. Langendorff-perfused isolated rat hearts were subjected to 25 min global ischemia followed by 45 min reperfusion, and recovery of energy metabolism as well as functional cardiac parameters were monitored. Although to varying extents, all substances improved recovery of creatine phosphate, ATP, intracellular pH, and reutilization of inorganic phosphate. These favorable changes were accompanied by improved recovery of heart function parameters and reduced infarct size. In addition and again to varying extents, all studied substances decreased oxidative damage (lipid peroxidation and protein oxidation), and activated Akt, glycogen synthase kinase (GSK)-3beta, and ERK1/2. Correlation between cardioprotective and kinase activating effectivity of the compounds proved to be statistically significant. Physiological significance of these kinase activations was established by demonstrating that inhibition of Akt by LY294002 and ERK1/2 by PD98059 compromised the cardioprotective effect of all the substances studied. In conclusion, we demonstrated for the first time that activation of phosphatidylinositol-3-kinase (PI-3K)-Akt and ERK2 pathways significantly contributed to cardioprotective effects of a Ca(2+) antagonist and a beta-adrenergic receptor blocker. Furthermore, we found a strong correlation between cardioprotective and kinase-activating potencies of the substances studied (Verapamil, Metoprolol and two PARP inhibitors), which indicated the potentiality of these kinases as drug-targets in the therapy of ischemic heart disease. 相似文献
83.
Images of human erythrocytes from a healthy donor were recorded under differential interference contrast (DIC) microscopy;
they were acquired rapidly (~336 Hz) and the intensity of the centermost pixel of each cell was recorded for ~60 s (20,000
values). Various techniques were used to analyze the data, including detrended fluctuation analysis (DFA) and multiscale entropy
(MSE); however, power spectrum analysis was deemed the most appropriate for metrifying and comparing results. This analysis
was used to compare cells from young and old populations, and after perturbing normal conditions, with changes in temperature,
adenosine triphosphate (ATP) concentration (using NaF, an inhibitor of glycolysis, and α-toxin, a pore-forming molecule used
to permeabilize red cells to ATP), and water transport rates [using glycerol, and p-chloromercuriphenylsulfonic acid (pCMBS) to inhibit aquaporins, AQPs]. There were measurable differences in the membrane
fluctuation characteristics in populations of young and old cells, but there was no significant change in the flickering time
series on changing the temperature of an individual cell, by depleting it of ATP, or by competing with the minor water exchange
pathway via AQP3 using glycerol. However, pCMBS, which inhibits AQP1, the major water exchange pathway, inhibited flickering
in all cells, and yet it was restored by the membrane intercalating species dibutyl phthalate (DBP). We developed a computer
model to simulate acquired displacement spectral time courses and to evaluate various methods of data analysis, and showed
how the flexibility of the membrane, as defined in the model, affects the flickering time course. 相似文献
84.
新疆北部白冠攀雀的巢与巢址选择 总被引:1,自引:0,他引:1
2008年4—7月,在新疆北部对白冠攀雀巢址选择进行了研究。白冠攀雀的营巢习性特殊,巢呈囊袋状,结构甚为精致。对于白冠攀雀巢的研究,采用总面积调查法,进行地毯式的搜寻,并结合标图法对其进行标记,绘制分布图。研究结果共发现巢125个,营巢位于于临近湖泊、河流等水域附近的柳树、杨树、桦树等阔叶树上。营巢树种以柳树为主,占68.80%。巢的高度平均为(5.3±2.5)m,营巢于乔木的中下部(约1/3处),约70%的巢离河边不足30 m。对于巢址选择的研究,将原始记录中与巢址选择有关的特征变量进行主成分分析,分析表明,影响白冠攀雀巢址选择的主要因素有4种,依次为:郁闭度因素(包括营巢树胸径、巢上郁闭度)、营巢树种因素(包括营巢树种、树高、巢位高度和乔木种类)、方位因素(包括距河边距离和巢向)、食物与巢材因素。 相似文献
85.
86.
Jan Rupp Lisa Pfleiderer Christiane Jugert Sonja Moeller Matthias Klinger Klaus Dalhoff Werner Solbach Steffen Stenger Tamas Laskay Ger van Zandbergen 《PloS one》2009,4(6)
Background
Intracellular pathogens have developed elaborate strategies for silent infection of preferred host cells. Chlamydia pneumoniae is a common pathogen in acute infections of the respiratory tract (e.g. pneumonia) and associated with chronic lung sequelae in adults and children. Within the lung, alveolar macrophages and polymorph nuclear neutrophils (PMN) are the first line of defense against bacteria, but also preferred host phagocytes of chlamydiae.Methodology/Principal Findings
We could show that C. pneumoniae easily infect and hide inside neutrophil granulocytes until these cells become apoptotic and are subsequently taken up by macrophages. C. pneumoniae infection of macrophages via apoptotic PMN results in enhanced replicative activity of chlamydiae when compared to direct infection of macrophages, which results in persistence of the pathogen. Inhibition of the apoptotic recognition of C. pneumoniae infected PMN using PS- masking Annexin A5 significantly lowered the transmission of chlamydial infection to macrophages. Transfer of apoptotic C. pneumoniae infected PMN to macrophages resulted in an increased TGF-ß production, whereas direct infection of macrophages with chlamydiae was characterized by an enhanced TNF-α response.Conclusions/Significance
Taken together, our data suggest that C. pneumoniae uses neutrophil granulocytes to be silently taken up by long-lived macrophages, which allows for efficient propagation and immune protection within the human host. 相似文献87.
Gareth A. Palidwor Sergey Shcherbinin Matthew R. Huska Tamas Rasko Ulrich Stelzl Anup Arumughan Raphaele Foulle Pablo Porras Luis Sanchez-Pulido Erich E. Wanker Miguel A. Andrade-Navarro 《PLoS computational biology》2009,5(3)
A growing number of solved protein structures display an elongated structural
domain, denoted here as alpha-rod, composed of stacked pairs of anti-parallel
alpha-helices. Alpha-rods are flexible and expose a large surface, which makes
them suitable for protein interaction. Although most likely originating by
tandem duplication of a two-helix unit, their detection using sequence
similarity between repeats is poor. Here, we show that alpha-rod repeats can be
detected using a neural network. The network detects more repeats than are
identified by domain databases using multiple profiles, with a low level of
false positives (<10%). We identify alpha-rod repeats in
approximately 0.4% of proteins in eukaryotic genomes. We then
investigate the results for all human proteins, identifying alpha-rod repeats
for the first time in six protein families, including proteins STAG1-3, SERAC1,
and PSMD1-2 & 5. We also characterize a short version of these repeats
in eight protein families of Archaeal, Bacterial, and Fungal species. Finally,
we demonstrate the utility of these predictions in directing experimental work
to demarcate three alpha-rods in huntingtin, a protein mutated in
Huntington''s disease. Using yeast two hybrid analysis and an
immunoprecipitation technique, we show that the huntingtin fragments containing
alpha-rods associate with each other. This is the first definition of domains in
huntingtin and the first validation of predicted interactions between fragments
of huntingtin, which sets up directions toward functional characterization of
this protein. An implementation of the repeat detection algorithm is available
as a Web server with a simple graphical output: http://www.ogic.ca/projects/ard. This can be further visualized
using BiasViz, a graphic tool for representation of multiple sequence
alignments. 相似文献
88.
Biftu T Feng D Fisher M Liang GB Qian X Scribner A Dennis R Lee S Liberator PA Brown C Gurnett A Leavitt PS Thompson D Mathew J Misura A Samaras S Tamas T Sina JF McNulty KA McKnight CG Schmatz DM Wyvratt M 《Bioorganic & medicinal chemistry letters》2006,16(9):2479-2483
Compounds 10a (IC50 110 pM) and 21 (IC50 40 pM) are the most potent inhibitors of Eimeria tenella cGMP-dependent protein kinase activity reported to date and are efficacious in the in vivo antiparasitic assay when administered to chickens at 12.5 and 6.25 ppm levels in the feed. However, both compounds are positive in the Ames microbial mutagenesis assay which precludes them from further development as antiprotozoal agents in the absence of negative lifetime rodent carcinogenicity studies. 相似文献
89.
Feng D Fisher M Liang GB Qian X Brown C Gurnett A Leavitt PS Liberator PA Mathew J Misura A Samaras S Tamas T Schmatz DM Wyvratt M Biftu T 《Bioorganic & medicinal chemistry letters》2006,16(23):5978-5981
Compounds 10a-10d and 10i are very potent inhibitors of Eimeria tenella cGMP-dependent protein kinase (0.081-0.32 nM) and are very efficacious antiparasitic agents in vivo when administered to chickens at 12.5-25 ppm levels in the feed. 相似文献
90.
Presence of Anti-Microbial Antibodies in Liver Cirrhosis – A Tell-Tale Sign of Compromised Immunity?
Papp M Norman GL Vitalis Z Tornai I Altorjay I Foldi I Udvardy M Shums Z Dinya T Orosz P Lombay B Par G Par A Veres G Csak T Osztovits J Szalay F Lakatos PL 《PloS one》2010,5(9):e12957