全文获取类型
收费全文 | 627篇 |
免费 | 49篇 |
出版年
2022年 | 6篇 |
2021年 | 10篇 |
2020年 | 6篇 |
2019年 | 6篇 |
2018年 | 10篇 |
2017年 | 10篇 |
2016年 | 12篇 |
2015年 | 35篇 |
2014年 | 32篇 |
2013年 | 34篇 |
2012年 | 46篇 |
2011年 | 41篇 |
2010年 | 32篇 |
2009年 | 35篇 |
2008年 | 41篇 |
2007年 | 30篇 |
2006年 | 30篇 |
2005年 | 22篇 |
2004年 | 27篇 |
2003年 | 25篇 |
2002年 | 26篇 |
2001年 | 6篇 |
1999年 | 10篇 |
1998年 | 5篇 |
1997年 | 7篇 |
1996年 | 4篇 |
1995年 | 7篇 |
1994年 | 4篇 |
1993年 | 7篇 |
1992年 | 4篇 |
1991年 | 6篇 |
1990年 | 6篇 |
1989年 | 3篇 |
1988年 | 7篇 |
1985年 | 3篇 |
1984年 | 3篇 |
1983年 | 4篇 |
1982年 | 3篇 |
1980年 | 9篇 |
1979年 | 4篇 |
1978年 | 5篇 |
1975年 | 5篇 |
1973年 | 5篇 |
1972年 | 4篇 |
1971年 | 6篇 |
1970年 | 3篇 |
1968年 | 4篇 |
1967年 | 5篇 |
1966年 | 5篇 |
1965年 | 3篇 |
排序方式: 共有676条查询结果,搜索用时 156 毫秒
61.
A. Sverdrup E. Kjellsby ‡ P. G. Krüger † R. Fløysand F. R. Knudsen § P. S. Enger § G. Serck-Hanssen K. B. Helle 《Journal of fish biology》1994,45(6):973-995
The postulated harmful effects of underwater detonations of explosives on the vascular endothelium in farmed Atlantic salmon were assessed under controlled conditions. Acclimated salmon were exposed to a series of 10 underwater explosions over 70 min, each of ≃2 MPa in pressure amplitude, in a laboratory tank. No mortality occurred immediately or during the subsequent 7 days of observation. The response to each of the 10 detonations was cessation of swimming for a few minutes and failure to express a flight reaction.
Structurally, the vascular endothelium of the ventral aorta (VA) and the coeliaco mesenteric artery (CMA) revealed signs of injury within the first 30 min after the experimental shock. In contrast to vessels from the controls, the injury was further aggravated by the mounting procedure for tension recording. The endothelial impairment was temporary, persisting throughout the first days while being restored after 1 week.
Functionally, the cholinergic and adrenergic vasoconstrictor responses in the CMA were markedly reduced during the first day after the shock. These responses were similar to those observed in the endothelium probed CMA of controls. The loss of structural integrity and the reduced functional responses indicated a temporary impairment of the vascular endothelium in response to this experimental simulation of a seismic shock.
The primary stress hormones, adrenaline and cortisol, were not immediately elevated in plasma, but revealed different patterns of delayed increases. The head kidney content of catecholamines was not altered by the acoustic shock, while the atrial uptake of both calecholamines declined progressively during the 48 h of observation. Plasma chloride was not affected. 相似文献
Structurally, the vascular endothelium of the ventral aorta (VA) and the coeliaco mesenteric artery (CMA) revealed signs of injury within the first 30 min after the experimental shock. In contrast to vessels from the controls, the injury was further aggravated by the mounting procedure for tension recording. The endothelial impairment was temporary, persisting throughout the first days while being restored after 1 week.
Functionally, the cholinergic and adrenergic vasoconstrictor responses in the CMA were markedly reduced during the first day after the shock. These responses were similar to those observed in the endothelium probed CMA of controls. The loss of structural integrity and the reduced functional responses indicated a temporary impairment of the vascular endothelium in response to this experimental simulation of a seismic shock.
The primary stress hormones, adrenaline and cortisol, were not immediately elevated in plasma, but revealed different patterns of delayed increases. The head kidney content of catecholamines was not altered by the acoustic shock, while the atrial uptake of both calecholamines declined progressively during the 48 h of observation. Plasma chloride was not affected. 相似文献
62.
Evidence for persistent, occult infection in neonatal macaques following perinatal transmission of simian-human immunodeficiency virus SF162P3 下载免费PDF全文
Jayaraman P Zhu T Misher L Mohan D Kuller L Polacino P Richardson BA Bielefeldt-Ohmann H Anderson D Hu SL Haigwood NL 《Journal of virology》2007,81(2):822-834
To model human immunodeficiency virus (HIV) perinatal transmission, we studied infection of simian-human immunodeficiency virus (SHIV) SF162P3 in 10 pregnant Macaca nemestrina females and their offspring. Four of nine infants born to and suckled by these dams had evidence of infection, a transmission rate of 44.4% (95% confidence interval, 13.7% to 78.8%). We quantified transplacentally acquired and de novo Env-specific immunoglobulin G (IgG), IgM, and neutralizing antibodies in newborns. Transmission of escape variants was confirmed. In utero infection (n = 1) resulted in high viremia, depletion of peripheral CD4+ T cells, and rapid evolution of env in blood and tissues. Peripartum or postpartum SHIV infection (n = 3) resulted in postacute viral control that was undetectable by very sensitive multiplex PCR, despite increasing antibodies. Seropositive infants with highly controlled viremia had homogeneous peripheral blood env sequences, and their tissues had <3 copies per million cells. A high incidence of seropositive virus-low or -negative SHIV infection in infant macaques has implications for HIV type 1 perinatal transmission and detection. 相似文献
63.
The neutralizing activity of anti-hepatitis C virus antibodies is modulated by specific glycans on the E2 envelope protein 总被引:5,自引:1,他引:4 下载免费PDF全文
Helle F Goffard A Morel V Duverlie G McKeating J Keck ZY Foung S Penin F Dubuisson J Voisset C 《Journal of virology》2007,81(15):8101-8111
Hepatitis C virus (HCV) envelope glycoproteins are highly glycosylated, with up to 5 and 11 N-linked glycans on E1 and E2, respectively. Most of the glycosylation sites on HCV envelope glycoproteins are conserved, and some of the glycans associated with these proteins have been shown to play an essential role in protein folding and HCV entry. Such a high level of glycosylation suggests that these glycans can limit the immunogenicity of HCV envelope proteins and restrict the binding of some antibodies to their epitopes. Here, we investigated whether these glycans can modulate the neutralizing activity of anti-HCV antibodies. HCV pseudoparticles (HCVpp) bearing wild-type glycoproteins or mutants at individual glycosylation sites were evaluated for their sensitivity to neutralization by antibodies from the sera of infected patients and anti-E2 monoclonal antibodies. While we did not find any evidence that N-linked glycans of E1 contribute to the masking of neutralizing epitopes, our data demonstrate that at least three glycans on E2 (denoted E2N1, E2N6, and E2N11) reduce the sensitivity of HCVpp to antibody neutralization. Importantly, these three glycans also reduced the access of CD81 to its E2 binding site, as shown by using a soluble form of the extracellular loop of CD81 in inhibition of entry. These data suggest that glycans E2N1, E2N6, and E2N11 are close to the binding site of CD81 and modulate both CD81 and neutralizing antibody binding to E2. In conclusion, this work indicates that HCV glycans contribute to the evasion of HCV from the humoral immune response. 相似文献
64.
Johansen ML Bak LK Schousboe A Iversen P Sørensen M Keiding S Vilstrup H Gjedde A Ott P Waagepetersen HS 《Neurochemistry international》2007,50(7-8):1042-1051
Cerebral hyperammonemia is a hallmark of hepatic encephalopathy, a debilitating condition arising secondary to liver disease. Pyruvate oxidation including tricarboxylic acid (TCA) cycle metabolism has been suggested to be inhibited by hyperammonemia at the pyruvate and -ketoglutarate dehydrogenase steps. Catabolism of the branched-chain amino acid isoleucine provides both acetyl-CoA and succinyl-CoA, thus by-passing both the pyruvate dehydrogenase and the -ketoglutarate dehydrogenase steps. Potentially, this will enable the TCA cycle to work in the face of ammonium-induced inhibition. In addition, this will provide the -ketoglutarate carbon skeleton for glutamate and glutamine synthesis by glutamate dehydrogenase and glutamine synthetase (astrocytes only), respectively, both reactions fixing ammonium. Cultured cerebellar neurons (primarily glutamatergic) or astrocytes were incubated in the presence of either [U-13C]glucose (2.5 mM) and isoleucine (1 mM) or [U-13C]isoleucine and glucose. Cell cultures were treated with an acute ammonium chloride load of 2 (astrocytes) or 5 mM (neurons and astrocytes) and incorporation of 13C-label into glutamate, aspartate, glutamine and alanine was determined employing mass spectrometry. Labeling from [U-13C]glucose in glutamate and aspartate increased as a result of ammonium-treatment in both neurons and astrocytes, suggesting that the TCA cycle was not inhibited. Labeling in alanine increased in neurons but not in astrocytes, indicating elevated glycolysis in neurons. For both neurons and astrocytes, labeling from [U-13C]isoleucine entered glutamate and aspartate albeit to a lower extent than from [U-13C]glucose. Labeling in glutamate and aspartate from [U-13C]isoleucine was decreased by ammonium treatment in neurons but not in astrocytes, the former probably reflecting increased metabolism of unlabeled glucose. In astrocytes, ammonia treatment resulted in glutamine production and release to the medium, partially supported by catabolism of [U-13C]isoleucine. In conclusion, i) neuronal and astrocytic TCA cycle metabolism was not inhibited by ammonium and ii) isoleucine may provide the carbon skeleton for synthesis of glutamate/glutamine in the detoxification of ammonium. 相似文献
65.
Hald H Naur P Pickering DS Sprogøe D Madsen U Timmermann DB Ahring PK Liljefors T Schousboe A Egebjerg J Gajhede M Kastrup JS 《The Journal of biological chemistry》2007,282(35):25726-25736
More than 50 structures have been reported on the ligand-binding core of the ionotropic glutamate receptor iGluR2 that belongs to the 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid-type of receptors. In contrast, the ligand-binding core of the kainic acid-type receptor iGluR5 has only been crystallized with three different ligands. Hence, additional structures of iGluR5 are needed to broaden the understanding of the ligand-binding properties of iGluR5, and the conformational changes leading to channel opening and closing. Here, we present two structures of the ligand-binding core of iGluR5; one as a complex with the partial agonist (2S,3S,4S)-3-carboxymethyl-4-[(1Z,3E,5R)-5-carboxy-1-methyl-hexa-1,3-dienyl]-pyrrolidine-2-carboxylic acid (domoic acid) and one as a complex with the antagonist (S)-2-amino-3-[5-tert-butyl-3-(phosphonomethoxy)-4-isoxazolyl]propionic acid ((S)-ATPO). In agreement with the partial agonist activity of domoic acid, the ligand-binding core of the iGluR5 complex is stabilized by domoic acid in a conformation that is 11 degrees more open than the conformation observed in the full agonist (S)-glutamic acid complex. This is primarily caused by the 5-carboxy-1-methyl-hexa-1,3-dienyl moiety of domoic acid and residues Val685-Thr690 of iGluR5. An even larger domain opening of 28 degrees is introduced upon binding of the antagonist (S)-ATPO. It appears that the span of domain opening is much larger in the ligand-binding core of iGluR5 (30 degrees) compared with what has been observed in iGluR2 (19 degrees ). Similarly, much larger variation in the distances between transmembrane linker residues in the two protomers comprising the dimer is observed in iGluR5 as compared with iGluR2. 相似文献
66.
67.
Martin Weigl Michael Grabner Gerhard Helle Gerhard H. Schleser Rupert Wimmer 《Dendrochronologia》2007,24(2-3):117-122
Axial variation of latewood-widths and -stable isotopes (δ13C and δ18O) of a single sessile oak tree (Quercus petraea (Matt.) Liebl.) was analyzed. The influence of sampling height was found to be weak for both, latewood-widths and -stable isotopes in the latewood. The observed trends with stem-height show clearly that possible effects due to cambial aging are overrated by annual effects. In addition, relations between samples from different stem-heights are strong for identical calendar years while they are poor for identical cambial age. This indicates that samples from both, living trees and historical wood can be taken from any height position of a trunk or beam as long they are free from anatomical abnormities. Simple correlation and Gleichläufigkeit were used for validation. 相似文献
68.
Koyi Choi Sabrina Batke Barnabas Szakal Jonathan Lowther Fanfan Hao Prabha Sarangi Dana Branzei Helle D. Ulrich Xiaolan Zhao 《Nucleic acids research》2015,43(5):2666-2677
Many genome maintenance factors have multiple enzymatic activities. In most cases, how their distinct activities functionally relate with each other is unclear. Here we examined the conserved budding yeast Rad5 protein that has both ubiquitin ligase and DNA helicase activities. The Rad5 ubiquitin ligase activity mediates PCNA poly-ubiquitination and subsequently recombination-based DNA lesion tolerance. Interestingly, the ligase domain is embedded in a larger helicase domain comprising seven consensus motifs. How features of the helicase domain influence ligase function is controversial. To clarify this issue, we use genetic, 2D gel and biochemical analyses and show that a Rad5 helicase motif important for ATP binding is also required for PCNA poly-ubiquitination and recombination-based lesion tolerance. We determine that this requirement is due to a previously unrecognized contribution of the motif to the PCNA and ubiquitination enzyme interaction, and not due to its canonical role in supporting helicase activity. We further show that Rad5′s helicase-mediated contribution to replication stress survival is separable from recombination. These findings delineate how two Rad5 enzymatic domains concertedly influence PCNA modification, and unveil their discrete contributions to stress tolerance. 相似文献
69.
Antonio Dobon Pilar Cordero Fatima Kreft Søren R. Østergaard Helle Antvorskov Mats Robertsson Maria Smolander Mercedes Hortal 《The International Journal of Life Cycle Assessment》2011,16(6):537-547
Purpose
This paper is the second part of a two-paper series dealing with the sustainability evaluation of a new communicative packaging concept. The communicative packaging concept includes a device that allows changing the expiry date of the product as function of temperature during transport and storage: a flexible best-before-date (FBBD). Such device was analysed in a consumer unit consisting of a nanoclay-based polylactic acid tray filled with pork chops. 相似文献70.