全文获取类型
收费全文 | 420篇 |
免费 | 25篇 |
国内免费 | 2篇 |
出版年
2024年 | 1篇 |
2023年 | 1篇 |
2022年 | 5篇 |
2021年 | 16篇 |
2020年 | 10篇 |
2019年 | 11篇 |
2018年 | 10篇 |
2017年 | 8篇 |
2016年 | 18篇 |
2015年 | 11篇 |
2014年 | 26篇 |
2013年 | 41篇 |
2012年 | 33篇 |
2011年 | 37篇 |
2010年 | 22篇 |
2009年 | 12篇 |
2008年 | 22篇 |
2007年 | 19篇 |
2006年 | 11篇 |
2005年 | 9篇 |
2004年 | 10篇 |
2003年 | 17篇 |
2002年 | 8篇 |
2001年 | 11篇 |
2000年 | 11篇 |
1999年 | 5篇 |
1998年 | 5篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1995年 | 4篇 |
1994年 | 7篇 |
1993年 | 2篇 |
1992年 | 7篇 |
1991年 | 4篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 6篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1977年 | 3篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1972年 | 1篇 |
1958年 | 1篇 |
排序方式: 共有447条查询结果,搜索用时 15 毫秒
41.
Minqin R Rajendran R Pan N Tan BK Ong WY Watt F Halliwell B 《Free radical biology & medicine》2005,38(9):1206-1211
Several epidemiological studies have suggested that increased iron stores are associated with increased atherosclerotic events. In order to test the hypothesis that decreasing the vascular level of iron slows lesion growth, we examined the effects of the iron chelator Desferal (72 mg/kg/day, 5 days/week) on atherosclerosis and lesion iron content in cholesterol-fed New Zealand White rabbits. Rabbits were fed with a 1% w/w cholesterol diet for either 8 weeks (and for the last 5 weeks injected daily with Desferal) or 12 weeks (and for the last 9 weeks injected with Desferal). Controls were injected with saline. A significant reduction in average lesion area (p = 0.038) was observed in the 12-week treated animals compared with the 12-week controls. The average lesion iron level of the 12-week treated animals (58 ppm dry wt) was also significantly lower (p = 0.030) than in 12-week control animals (95 ppm dry wt), as measured using nuclear microscopy with the combination of scanning transmission ion microscopy, Rutherford back-scattering spectroscopy, and particle-induced X-ray emission. No reduction in lesion area or iron content was observed in the 8-week treated animals compared with controls, and no change in lesion zinc concentration was observed for either group. Our data strengthen the concept that iron contributes to the early stages of the development of atherosclerosis. 相似文献
42.
Patients with systemic autoimmune diseases usually produce high levels of antibodies to self-antigens (autoantigens). The
repertoire of common autoantigens is remarkably limited, yet no readily understandable shared thread links these apparently
diverse proteins. Using computer prediction algorithms, we have found that most nuclear systemic autoantigens are predicted
to contain long regions of extreme structural disorder. Such disordered regions would generally make poor B cell epitopes
and are predicted to be under-represented as potential T cell epitopes. Consideration of the potential role of protein disorder
may give novel insights into the possible role of molecular mimicry in the pathogenesis of autoimmunity. The recognition of
extreme autoantigen protein disorder has led us to an explicit model of epitope spreading that explains many of the paradoxical
aspects of autoimmunity – in particular, the difficulty in identifying autoantigen-specific helper T cells that might collaborate
with the B cells activated in systemic autoimmunity. The model also explains the experimentally observed breakdown of major
histocompatibility complex (MHC) class specificity in peptides associated with the MHC II proteins of activated autoimmune
B cells, and sheds light on the selection of particular T cell epitopes in autoimmunity. Finally, the model helps to rationalize
the relative rarity of clinically significant autoimmunity despite the prevalence of low specificity/low avidity autoantibodies
in normal individuals. 相似文献
43.
Rajendran V Pu YS Chen BH 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2005,824(1-2):99-106
An HPLC method was developed to determine the various carotenoids in human serum. A C-30 column and a mobile phase of 100% methanol (A) and 100% methylene chloride (B) with the following gradient elution were used: 90% A and 10% B in the beginning, maintained for 5 min, decreased to 78% A at 15 min, 62% A at 30 min, 52% A at 40 min, 41% A at 50 min, 38% A at 55 min, maintained for 3 min, and returned to 100% A at 65 min. A total of 21 carotenoids, including all-trans forms of lutein, zeaxanthin, alpha-cryptoxanthin, beta-cryptoxanthin, alpha-carotene, beta-carotene and lycopene, as well as their 14 cis-isomers were resolved within 51 min at a flow rate of 1.0 mL/min and detection at 476 nm. all-trans-beta-Carotene was found to be present in highest amount (256.3-864.2 ng/mL), followed by all-trans-lycopene (64.4-569.2 ng/mL), all-trans-lutein (137.9-450.3 ng/mL), all-trans-alpha-cryptoxanthin (55.7-188.2 ng/mL), all-trans-beta-cryptoxanthin (43.1-134.5 ng/mL), all-trans-alpha-carotene (20.0-122.1 ng/mL) and all-trans-zeaxanthin (9.1-21.3 ng/mL). Similar trend was observed for cis-isomers of carotenoids. 相似文献
44.
45.
46.
Mutations in SOD1 cause FALS by a gain of function likely related to protein misfolding and aggregation. SOD1 mutations encompass virtually every domain of the molecule, making it difficult to identify motifs important in SOD1 aggregation. Zinc binding to SOD1 is important for structural integrity, and is hypothesized to play a role in mutant SOD1 aggregation. To address this question, we mutated the unique zinc binding sites of SOD1 and examined whether these changes would influence SOD1 aggregation. We generated single and multiple mutations in SOD1 zinc binding residues (H71, H80 and D83) either alone or in combination with an aggregate forming mutation (A4V) known to cause disease. These SOD1 mutants were assayed for their ability to form aggregates.Using an in vitro cellular SOD1 aggregation assay, we show that combining A4V with mutations in non-zinc binding domains (G37R or G85R) increases SOD1 aggregation potential. Mutations at two zinc binding residues (H71G and D83G) also increase SOD1 aggregation potential. However, an H80G mutation at the third zinc binding residue decreases SOD1 aggregation potential even in the context of other aggregate forming SOD1 mutations. These results demonstrate that various mutations have different effects on SOD1 aggregation potential and that the H80G mutation appears to uniquely act as a dominant inhibitor of SOD1 aggregation. 相似文献
47.
48.
cAMP induces both active Cl(-) and active K(+) secretion in mammalian colon. It is generally assumed that a mechanism for K(+) exit is essential to maintain cells in the hyperpolarized state, thus favoring a sustained Cl(-) secretion. Both Kcnn4c and Kcnma1 channels are located in colon, and this study addressed the questions of whether Kcnn4c and/or Kcnma1 channels mediate cAMP-induced K(+) secretion and whether cAMP-induced K(+) secretion provides the driving force for Cl(-) secretion. Forskolin (FSK)-enhanced short-circuit current (indicator of net electrogenic ion transport) and K(+) fluxes were measured simultaneously in colonic mucosa under voltage-clamp conditions. Mucosal Na(+) orthovanadate (P-type ATPase inhibitor) inhibited active K(+) absorption normally present in rat distal colon. In the presence of mucosal Na(+) orthovanadate, serosal FSK induced both K(+) and Cl(-) secretion. FSK-induced K(+) secretion was 1) not inhibited by either mucosal or serosal 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34; a Kcnn4 channel blocker), 2) inhibited (92%) by mucosal iberiotoxin (Kcnma1 channel blocker), and 3) not affected by mucosal cystic fibrosis transmembrane conductance regulator inhibitor (CFTR(inh)-172). By contrast, FSK-induced Cl(-) secretion was 1) completely inhibited by serosal TRAM-34, 2) not inhibited by either mucosal or serosal iberiotoxin, and 3) completely inhibited by mucosal CFTR(inh)-172. These results indicate that cAMP-induced colonic K(+) secretion is mediated via Kcnma1 channels located in the apical membrane and most likely contributes to stool K(+) losses in secretory diarrhea. On the other hand, cAMP-induced colonic Cl(-) secretion requires the activity of Kcnn4b channels located in the basolateral membrane and is not dependent on the concurrent activation of apical Kcnma1 channels. 相似文献
49.
van Versendaal D Rajendran R Saiepour MH Klooster J Smit-Rigter L Sommeijer JP De Zeeuw CI Hofer SB Heimel JA Levelt CN 《Neuron》2012,74(2):374-383
During development, cortical plasticity is associated with the rearrangement of excitatory connections. While these connections become more stable with age, plasticity can still be induced in the adult cortex. Here we provide evidence that structural plasticity of?inhibitory synapses onto pyramidal neurons is?a major component of plasticity in the adult neocortex. In?vivo two-photon imaging was used to monitor the formation and elimination of fluorescently labeled inhibitory structures on pyramidal neurons. We find that ocular dominance plasticity in the adult visual cortex is associated with rapid inhibitory synapse loss, especially of those present on dendritic spines. This occurs not only with monocular deprivation but also with subsequent restoration of binocular vision. We propose that in the adult visual cortex the experience-induced loss of inhibition may effectively strengthen specific visual inputs with limited need for rearranging the excitatory circuitry. 相似文献
50.
The aim of present study was to isolate an iridoid glucoside from the leaves of Vitex negundo and evaluates its effects on dearrangement in plasma and tissues glycoprotein components in streptozotocin-induced diabetic rats. The levels of blood glucose, plasma and tissues glycoproteins such as hexose, hexosamine, fucose and sialic acid were significantly increased whereas plasma insulin levels were significantly decreased in diabetic rats. On oral administration of iridoid glucoside at a concentration of 50 mg/kg b.w. once daily to diabetic rats for the period of 30 days, reversed the above-mentioned hyperglycemia-induced biochemical changes to near normal levels. The anti-hyperglycemic effect of iridoid glucoside was comparable with glibenclamide, a known hypoglycemic drug. Based on the results obtained from the present study, it may be concluded that iridoid glucoside possesses significant productive effect on glycoprotein metabolism in addition to its antidiabetic effect. 相似文献