全文获取类型
收费全文 | 288篇 |
免费 | 10篇 |
专业分类
298篇 |
出版年
2021年 | 6篇 |
2018年 | 4篇 |
2017年 | 5篇 |
2016年 | 4篇 |
2015年 | 13篇 |
2014年 | 9篇 |
2013年 | 15篇 |
2012年 | 14篇 |
2011年 | 16篇 |
2010年 | 7篇 |
2009年 | 11篇 |
2008年 | 10篇 |
2007年 | 12篇 |
2006年 | 13篇 |
2005年 | 7篇 |
2004年 | 18篇 |
2003年 | 18篇 |
2002年 | 12篇 |
2001年 | 2篇 |
2000年 | 3篇 |
1999年 | 2篇 |
1998年 | 8篇 |
1997年 | 4篇 |
1996年 | 6篇 |
1995年 | 2篇 |
1994年 | 4篇 |
1993年 | 3篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1989年 | 2篇 |
1988年 | 6篇 |
1987年 | 4篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1981年 | 4篇 |
1980年 | 5篇 |
1979年 | 3篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1976年 | 3篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1967年 | 2篇 |
1966年 | 1篇 |
1965年 | 1篇 |
1955年 | 1篇 |
排序方式: 共有298条查询结果,搜索用时 0 毫秒
101.
Peripheral arterial disease (PAD) is a common, progressive manifestation of atherothrombotic vascular disease, which should be managed no different to cardiac disease. Indeed, there is growing evidence that PAD patients are a high risk group, although still relatively under-detected and under treated. This is despite the fact that PAD patients are an increased mortality rate comparable to those with pre-existing or established cardiovascular disease [myocardial infarction, stroke]. With a holistic approach to atherothrombotic vascular disease, our management of PAD can only get better. 相似文献
102.
Kuzmin Alexander I.; Lakomkin Vladimir L.; Kapelko Valeri I.; Vassort Guy 《American journal of physiology. Cell physiology》1998,275(3):C766
With the aim of estimating interstitial levels and the breakdownprocess of ATP, cardiac microdialysis was performed in the leftventricular wall of in situ control and postinfarcted as well as ofisolated, Langendorff-perfused rat hearts. With the use of abioluminescence technique for dialysate ATP measurement, the baselineinterstitial fluid ATP concentration in in situ hearts was estimated tobe 38 ± 8 nM. Regional ischemia induced an early peakincrease in interstitial fluid ATP to 373 ± 73 nM thatcorrelates with the maximal incidence of ventricular arrhythmias.During continuous infusion of individual adenine nucleotides (50 µMATP, ADP, or AMP), the dialysate samples were analyzed for adenine nucleotides, nucleosides, and bases using HPLC with ultraviolet detection. The patterns of catabolites were consistent with the majorpathway of metabolism, that is, sequential dephosphorylation catalyzedby a chain of separate ecto-nucleotidases. In in situ postinfarctedhearts as well as in perfused hearts, a reduced catabolism rate ofextracellular adenine nucleotides was observed. In conclusion, in insitu rat hearts, ATP can be released in substantial amounts in theinterstitium where it readily undergoes enzymatic degradation.Dephosphorylation occurs sequentially and faster in in situ controlhearts than in in situ postinfarcted or in perfused hearts. 相似文献
103.
Wei Wang John M. Lester Anthony E. Amorosa Deborah L. Chance Valeri V. Mossine Thomas P. Mawhinney 《Journal of visualized experiments : JoVE》2015,(100)
Synthetic glycopolymers are instrumental and versatile tools used in various biochemical and biomedical research fields. An example of a facile and efficient synthesis of well-controlled fluorescent statistical glycopolymers using reversible addition-fragmentation chain-transfer (RAFT)-based polymerization is demonstrated. The synthesis starts with the preparation of β-galactose-containing glycomonomer 2-lactobionamidoethyl methacrylamide obtained by reaction of lactobionolactone and N-(2-aminoethyl) methacrylamide (AEMA). 2-Gluconamidoethyl methacrylamide (GAEMA) is used as a structural analog lacking a terminal β-galactoside. The following RAFT-mediated copolymerization reaction involves three different monomers: N-(2-hydroxyethyl) acrylamide as spacer, AEMA as target for further fluorescence labeling, and the glycomonomers. Tolerant of aqueous systems, the RAFT agent used in the reaction is (4-cyanopentanoic acid)-4-dithiobenzoate. Low dispersities (≤1.32), predictable copolymer compositions, and high reproducibility of the polymerizations were observed among the products. Fluorescent polymers are obtained by modifying the glycopolymers with carboxyfluorescein succinimidyl ester targeting the primary amine functional groups on AEMA. Lectin-binding specificities of the resulting glycopolymers are verified by testing with corresponding agarose beads coated with specific glycoepitope recognizing lectins. Because of the ease of the synthesis, the tight control of the product compositions and the good reproducibility of the reaction, this protocol can be translated towards preparation of other RAFT-based glycopolymers with specific structures and compositions, as desired. 相似文献
104.
Valeri A Alonso-Ferrero ME Río P Pujol MR Casado JA Pérez L Jacome A Agirre X Calasanz MJ Hanenberg H Surrallés J Prosper F Albella B Bueren JA 《PloS one》2010,5(12):e15525
Chronic myeloid leukemia (CML) is a malignant clonal disorder of the hematopoietic system caused by the expression of the BCR/ABL fusion oncogene. Although it is well known that CML cells are genetically unstable, the mechanisms accounting for this genomic instability are still poorly understood. Because the Fanconi anemia (FA) pathway is believed to control several mechanisms of DNA repair, we investigated whether this pathway was disrupted in CML cells. Our data show that CML cells have a defective capacity to generate FANCD2 nuclear foci, either in dividing cells or after DNA damage. Similarly, human cord blood CD34(+) cells transduced with BCR/ABL retroviral vectors showed impaired FANCD2 foci formation, whereas FANCD2 monoubiquitination in these cells was unaffected. Soon after the transduction of CD34(+) cells with BCR/ABL retroviral vectors a high proportion of cells with supernumerary centrosomes was observed. Similarly, BCR/ABL induced a high proportion of chromosomal abnormalities, while mediated a cell survival advantage after exposure to DNA cross-linking agents. Significantly, both the impaired formation of FANCD2 nuclear foci, and also the predisposition of BCR/ABL cells to develop centrosomal and chromosomal aberrations were reverted by the ectopic expression of BRCA1. Taken together, our data show for the first time a disruption of the FA/BRCA pathway in BCR/ABL cells, suggesting that this defective pathway should play an important role in the genomic instability of CML by the co-occurrence of centrosomal amplification and DNA repair deficiencies. 相似文献
105.
Valeri Pawlowski 《Inorganica chimica acta》2004,357(3):824-826
The mixed-valence compound [CuI(dmp)2][CuII(hfac)3] with dmp=2,9-dimethyl-1,10-phenanthroline and hfac−=hexafluoroacetylacetonate has been synthesized and structurally characterized by X-ray crystallography. The MV interaction has been examined by emission spectroscopy. The phosphorescence of [CuI(dmp)2]+ is completely quenched. It is suggested that this quenching takes place by excited state electron transfer from Cu(I) to Cu(II). 相似文献
106.
Intramolecular fluorescence quenching of cyanine dyes was investigated using a model hairpin oligonucleotide decoy encoding a NF-kappaB p50 subunit binding site. Two types of hairpin oligonucleotides were synthesized: (1) 5'-(6-aminohexyl)- and 3'-(3-aminopropyl)-linked (I); (2) 5'-(6-aminohexyl)- and 3'-[3-(3-hydroxypropyldithio)propyl]-linked (II). Oligonucleotide I was covalently modified using monofunctional either Cy3- or Cy5.5-N-hydroxysuccinimide esters. Using reverse-phase HPLC, mono-and dicyanineamide derivatives of I were isolated. Mono-Cy3-modified derivatives of I, but not the mono-Cy5.5-modified derivatives, showed a 2-fold higher Cy3 fluorescence intensity compared to the free dye. There was no detectable difference in fluorescence between the di-Cy3 derivative of I and the free dye at the same concentration. However, there was a 4-fold quenching of fluorescence in the case of the di-Cy5.5 derivative of the same hairpin oligonucleotide. The quenching of Cy5.5 fluorescence could not be explained by the interaction of Cy5.5 with nucleotide bases as demonstrated by incubating free Cy5.5 dye with oligonuclotides. The quenching effect was further investigated using an oligonucleotide bearing a cleavable 3'-amino-terminated linker bearing an S-S bond (III). After modification of the 5'- and 3'-end of oligonucleotide III with a Cy5.5 monofunctional hydroxysuccinimide ester, a 70-75% quenching of fluorescence was observed. Fluorescence was 100% dequenched after the reduction of S-S bond. The obtained result unequivocally demonstrates that the formation of intramolecular Cy5.5 dimers is the dominant mechanism of fluorescence quenching in symmetric dye-dye hairpin decoy beacons. 相似文献
107.
Beck V Jabůrek M Breen EP Porter RK Jezek P Pohl EE 《Biochimica et biophysica acta》2006,1757(5-6):474-479
Electrophysiological characterisation of the vast number of annotated channel and transport proteins in the postgenomic era would be greatly facilitated by the introduction of rapid and robust methods for the functional incorporation of membrane proteins into defined lipid bilayers. Here, we describe an automated technique for reconstitution of membrane proteins into lipid bilayer membranes, which substantially reduces both the reconstitution time and the amount of protein required for the membrane formation. The method allows the investigation of single protein channels as well as insertion of multiple copies (approximately 10(7)) into a single bilayer. Despite a comparatively large membrane area (up to 300 microm diameter), the high stability of the membrane permits the application of transmembrane voltages up to 300 mV. This feature is especially important for studies of inner membrane mitochondrial proteins, since they act at potentials up to approximately 200 mV under physiological conditions. It is a combination of these advantages that enables the detailed investigation of the minuscule single protein conductances typical for proton transporters. We have applied the new technique for the reconstitution and electrophysiological characterisation of human recombinant uncoupling protein 1, hUCP1, that has been overexpressed in E. coli and purified from inclusion bodies. We demonstrate that hUCP1 activity in the presence of fatty acids is comparable to the activity of UCP1 isolated from brown adipose tissue. 相似文献
108.
L da Silva Lopes RB Marques HB Fernandes S da Silva Pereira MC Ayres MH Chaves FR Almeida 《Journal of biomedical science》2012,19(1):68-6
ABSTRACT: BACKGROUND: The mechanisms of the antinociceptive activity of () epicatechin (EPI), a compound isolated from the hydroalcoholic fraction of Combreum leprosum Mart & Eicher. METHODS: were assessed in the model of chemical nociception induced by glutamate (20 mumol/paw). To evaluate the mechanisms involved, the animals , male Swiss mice (25-30 g), received EPI (50 mg/kg p.o.) after pretreatment with naloxone (2 mg/kg s.c. opioid antagonist), glibenclamide (2 mg/kg s.c. antagonist K + channels sensitive to ATP), ketanserin (0.3 mg/kg s.c. antagonist of receptor 5-HT2A), yoimbine (0.15 mg/kg s.c. alpha2 adrenergic receptor antagonist), pindolol (1 mg/kg s.c. 5-HT1a/1b receptor antagonist), atropine (0.1 mg/kg s.c. muscarinic antagonist) and caffeine (3 mg/kg s.c. adenosine receptor antagonist), ondansetron (0.5 mg/kg s.c. for 5-HT3 receptor) and L-arginine (600 mg/kg i.p.). RESULTS: The antinociceptive effect of EPI was reversed by pretreatment with naloxone and glibenclamide, ketanserin, yoimbine, atropine and pindolol, which demonstrates the involvement of opioid receptors and potassium channels sensitive to ATP, the serotoninergic (receptor 5HT1A and 5HT2A), adrenergic (receptor alpha 2) and cholinergic (muscarinic receptor) systems in the activities that were observed. The effects of EPI, however, were not reversed by pretreatment with caffeine, L-arginine or ondansetron, which shows that there is no involvement of 5HT3 receptors or the purinergic and nitrergic systems in the antinociceptive effect of EPI. In the Open Field and Rotarod test, EPI had no significant effect, which shows that there was no central nervous system depressant or muscle relaxant effect on the results. CONCLUSIONS: This study demonstrates that the antinociceptive activity of EPI in the glutamate model involves the participation of the opioid system, serotonin, adrenergic and cholinergic. 相似文献
109.
Anne Rupprecht Elena A. Sokolenko Valeri Beck Olaf Ninnemann Thorsten Trimbuch Petr Jezek Elena E. Pohl 《Biophysical journal》2010,98(8):1503-1511
The molecular mechanism responsible for the regulation of the mitochondrial membrane proton conductance (G) is not clearly understood. This study investigates the role of the transmembrane potential (ΔΨm) using planar membranes, reconstituted with purified uncoupling proteins (UCP1 and UCP2) and/or unsaturated FA. We show that high ΔΨm (similar to ΔΨm in mitochondrial State IV) significantly activates the protonophoric function of UCPs in the presence of FA. The proton conductance increases nonlinearly with ΔΨm. The application of ΔΨm up to 220 mV leads to the overriding of the protein inhibition at a constant ATP concentration. Both, the exposure of FA-containing bilayers to high ΔΨm and the increase of FA membrane concentration bring about the significant exponential Gm increase, implying the contribution of FA in proton leak. Quantitative analysis of the energy barrier for the transport of FA anions in the presence and absence of protein suggests that FA− remain exposed to membrane lipids while crossing the UCP-containing membrane. We believe this study shows that UCPs and FA decrease ΔΨm more effectively if it is sufficiently high. Thus, the tight regulation of proton conductance and/or FA concentration by ΔΨm may be key in mitochondrial respiration and metabolism. 相似文献
110.
Paolo Alfieri Francesco Scibelli Lorenzo Sinibaldi Giovanni Valeri Cristina Caciolo Roberta Lucia Novello Antonio Novelli Maria Cristina Digilio Marco Tartaglia Stefano Vicari 《Genes, Brain & Behavior》2020,19(7)
Increasing evidence links heterozygosity for NRXN1 gene deletions to a clinically wide spectrum of neurodevelopmental, psychiatric, and neurological disorders. However, to date, the neurocognitive and social communication features of children carrying this genomic rearrangement have not been assessed in detail. The cognitive and behavioral profiles of five children carrying a heterozygous NRXN1 deletion were investigated through systematic assessment of the cognitive and developmental levels, adaptive profile and presence of behavioral symptoms and autistic features. Furthermore, four transmitting parents were assessed by means of cognitive, psychopathological and parental stress tests. A below‐average cognitive level was documented in all children, and defective adaptive levels were observed in four of them. Three of the five children were diagnosed as having autism spectrum disorder in comorbidity with intellectual disability/global developmental delay, with a major impairment in social communication skills. The remaining two children presented with isolated intellectual disability and an unclassifiable neurodevelopmental disorder, respectively. This study provide data contributing to a more accurate characterization of the neurobehavioral phenotype of individuals carrying heterozygous NRXN1 deletions. This analysis indicates that these structural rearrangements are associated with a variable expression of neuropsychiatric symptoms, and cast some doubts about the incomplete penetrance of the disorder. 相似文献