全文获取类型
收费全文 | 11747篇 |
免费 | 1043篇 |
国内免费 | 318篇 |
出版年
2024年 | 37篇 |
2023年 | 239篇 |
2022年 | 327篇 |
2021年 | 474篇 |
2020年 | 468篇 |
2019年 | 624篇 |
2018年 | 434篇 |
2017年 | 401篇 |
2016年 | 370篇 |
2015年 | 421篇 |
2014年 | 653篇 |
2013年 | 860篇 |
2012年 | 473篇 |
2011年 | 490篇 |
2010年 | 413篇 |
2009年 | 421篇 |
2008年 | 466篇 |
2007年 | 430篇 |
2006年 | 397篇 |
2005年 | 318篇 |
2004年 | 346篇 |
2003年 | 300篇 |
2002年 | 307篇 |
2001年 | 253篇 |
2000年 | 181篇 |
1999年 | 199篇 |
1998年 | 201篇 |
1997年 | 181篇 |
1996年 | 152篇 |
1995年 | 161篇 |
1994年 | 181篇 |
1993年 | 125篇 |
1992年 | 179篇 |
1991年 | 148篇 |
1990年 | 149篇 |
1989年 | 150篇 |
1988年 | 163篇 |
1987年 | 122篇 |
1986年 | 97篇 |
1985年 | 132篇 |
1984年 | 153篇 |
1983年 | 109篇 |
1982年 | 105篇 |
1981年 | 99篇 |
1980年 | 66篇 |
1979年 | 41篇 |
1978年 | 17篇 |
1977年 | 19篇 |
1976年 | 14篇 |
1972年 | 11篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
981.
Expression and function of phospholipase A(2) in brain 总被引:2,自引:0,他引:2
Phospholipase A(2) (PLA(2)) appears to play a fundamental role in cell injury in the central nervous system. We have investigated PLA(2) expression in the astrocytoma cell line 1231N1, and found that GIVA, GIVB, GIVC and GVI PLA(2) messages are expressed. PLA(2) activity is increased by inflammatory/injury stimuli such as interleukin-1beta and lipopolysaccharide in these cells but with very different time courses. The arachidonic acid liberated is converted to prostaglandin E(2), possibly by cyclooxygenase-2, which is induced by inflammatory stimuli. This cell system emerges as a model to study injury/inflammation-related activation of the new PLA(2) forms GIVB and GIVC. 相似文献
982.
Ribonucleotide reductases (RNRs) are uniquely responsible for converting nucleotides to deoxynucleotides in all dividing
cells. The three known classes of RNRs operate through a free radical mechanism but differ in the way in which the protein
radical is generated. Class I enzymes depend on oxygen for radical generation, class II uses adenosylcobalamin, and the anaerobic
class III requires S-adenosylmethionine and an iron–sulfur cluster. Despite their metabolic prominence, the evolutionary origin and relationships
between these enzymes remain elusive. This gap in RNR knowledge can, to a major extent, be attributed to the fact that different
RNR classes exhibit greatly diverged polypeptide chains, rendering homology assessments inconclusive. Evolutionary studies
of RNRs conducted until now have focused on comparison of the amino acid sequence of the proteins, without considering how
they fold into space. The present study is an attempt to understand the evolutionary history of RNRs taking into account their
three-dimensional structure. We first infer the structural alignment by superposing the equivalent stretches of the three-dimensional
structures of representatives of each family. We then use the structural alignment to guide the alignment of all publicly
available RNR sequences. Our results support the hypothesis that the three RNR classes diverged from a common ancestor currently
represented by the anaerobic class III. Also, lateral transfer appears to have played a significant role in the evolution
of this protein family. 相似文献
983.
A lateral bud growth inhibitor was isolated from etiolated pea seedlings and identified as indole-3-aldehyde. The indole-3-aldehyde content was significantly higher in the diffusates from explants with apical bud and indole-3-acetic acid treated decapitated explants, in which apical dominance is maintained, than in those from decapitated ones releasing apical dominance. When the indole-3-aldehyde was applied to the cut surface of etiolated decapitated plants or directly to the lateral buds, it inhibited outgrowth of the latter. These results suggest that indole-3-aldehyde plays an important role as a lateral bud growth inhibitor in apical dominance of pea seedlings. 相似文献
984.
Summary. Dynorphin is a neuropeptide that is present in high quantities in the dorsal horn of the spinal cord. The peptide is actively
involved in pain processing pathways. However, its involvement in spinal cord injury is not well known. Alteration in dynorphin
immunoreactivity occurs following a focal trauma to the rat spinal cord. Infusion of dynorphin into the intrathecal space
of the cord results in ischemia, cell damage and abnormal motor function. Antibodies to dynorphin when injected into the intrathecal
space of the spinal cord following trauma improve motor recovery, reduce edema and cell changes. However, influence of dynorphin
on trauma induced alteration in spinal cord bioelectrical activity is still not known. Spinal cord evoked potentials (SCEP)
are good indicator of spinal cord pathology following trauma. Therefore, in present investigation, influence of dynorphin
antibodies on trauma induced changes in SCEP were examined in our rat model. In addition, spinal cord edema formation, microvascular
permeability disturbances and cell injury were also investigated. Our results show that topical application of dynorphin antiserum
(1 : 200) two min before injury markedly attenuated the SCEP changes immediately after injury. In the antiserum treated animals,
a significant reduction in the microvascular permeability, edema formation and cell injury was observed in the traumatised
spinal cord. These observations suggest that (i) dynorphin is involved in the altered bioelectrical activity of the spinal
cord following trauma, (ii) the peptide actively participates in the pathophysiological processes of cell injury in the spinal
cord trauma, and (iii) the dynorphin antiserum has potential therapeutic value for the treatment of spinal cord injuries.
Received July 3, 2001 Accepted August 6, 2001 Published online July 31, 2002 相似文献
985.
Summary. The possibility that nitric oxide synthase (NOS) inhibitors influence dynorphin immunoreactivity following hyperthermia was
examined in a rat model using a pharmacological approach. Previous reports from our laboratory show that hyperthermia induces
an upregulation of NOS in several brain regions that seems to be instrumental in causing cell injury. Recent reports suggest
that nitric oxide (NO) can influence dynorphin neurotransmission in the normal brain as well as in several pathological states.
Since dynorphin is neurotoxic in different animal models of brain or spinal cord injury, it may be that the peptide will contribute
to the cell injury in hyperthermia. The present investigation was carried out to determine whether hyperthermia can influence
dynorphin immunoreactivity in the brain, and if so, whether inhibition of NOS will influence the peptide distribution in the
brain following heat stress. Rats subjected to hyperthermia at 38°C for 4 h in a biological oxygen demand incubator (BOD)
resulted in a marked upregulation of dynorphin immunoreactivity in several brain regions e.g., cerebral cortex, hippocampus,
cerebellum and brain stem. Pretreatment of rats with two potent NOS inhibitors, L-NAME (30 mg/kg/day, i.p. for 7 days) or
L-NMMA (35 mg/kg/day, i.p. for 7 days) significantly attenuated the dynorphin immunoreactivity in the brain. These drugs were
also able to reduce hyperthermia induced blood-brain barrier (BBB) permeability, brain edema formation and cell injury. Taken
together, our results suggest that (i) hyperthermia has the capacity to upregulate dynorphin immunoreactivity in the brain,
(ii) inhibition of NOS considerably attenuates the dynorphin immunoreaction following heat stress and (iii) upregulation of
dynorphin is somehow contributing to hyperthermia induced brain damage, not reported earlier.
Received July 3, 2001 Accepted August 6, 2001 Published online July 31, 2002 相似文献
986.
Batrancourt B Levy R Lehericy S Hasboun D Samson Y Lavallée I Lamure M Dubois B 《Comptes rendus biologies》2002,325(4):439-455
This study proposes a closer look at the neuropsychological method defined as the study of the neural bases of the behavioural and cognitive functions using an organisation-representation model for current data and knowledge of the brain, and the application of an anatomofunctional database. A Centre of Cognitive Anatomy (CAC) was set up for the collection and processing of neuronatomical, neuropsychological, and psycho-behavioural data for patients presenting sequels of focal brain damage. Such a system would allow concurrent treatment of anatomical and functional data. We would expect the results from such a model to produce stable 'anatomofunctional laws' that would be independent of all inter-individual variations in the functioning of the brain and could be checked against the entire database of information. A direct application would be the improvement of cognitive and/or behavioural rehabilitation of patients with brain damage. 相似文献
987.
目的 :建立大鼠脑组织线粒体的体外蛋白合成体系并对其合成产物进行电泳分离和分子量鉴定。方法 :分离大鼠脑组织线粒体 ,用3 H 亮氨酸掺入法探索线粒体体外翻译的最佳条件 ,3 5S 蛋氨酸掺入并对翻译后产物经SDS 聚丙烯酰胺凝胶电泳和放射自显影进行分子量鉴定。结果 :分离的线粒体氧化磷酸化偶联程度高 ,呼吸控制率(RCR)在 3.5~ 5 .5之间 ;体外3 H 亮氨酸的掺入活性在 6 0min内近似线性增长 ,而后维持在一相对稳定水平 ;3 H 亮氨酸的掺入活性随线粒体蛋白浓度而增加 ,而单位线粒体蛋白的掺入活性在 1mg/ml时最高 ;3 5S 蛋氨酸掺入SDS 聚丙烯酰胺凝胶电泳后可观察到清晰的 8条自显影带 ,分子量分别为 (单位Kda) 86、6 6、5 6、43、33、2 9、2 5、18。结论 :用此方法建立的脑线粒体离体翻译反应体系具有高活性和翻译忠实性等特点 ,是研究脑mtDNA在翻译水平的表达及调控的有效方法 相似文献
988.
Hepatoprotective effects of Arctium lappa Linne on liver injuries induced by chronic ethanol consumption and potentiated by carbon tetrachloride 总被引:3,自引:0,他引:3
Lin SC Lin CH Lin CC Lin YH Chen CF Chen IC Wang LY 《Journal of biomedical science》2002,9(5):401-409
Arctium lappa Linne (burdock) is a perennial herb which is popularly cultivated as a vegetable. In order to evaluate its hepatoprotective effects, a group of rats (n = 10) was fed a liquid ethanol diet (4 g of absolute ethanol/ 80 ml of liquid basal diet) for 28 days and another group (n = 10) received a single intraperitoneal injection of 0.5 ml/kg carbon tetrachloride (CCl(4)) in order to potentiate the liver damage on the 21st day (1 day before the beginning of A. lappa treatment). Control group rats were given a liquid basal diet which did not contain absolute ethanol. When 300 mg/kg A. lappa was administered orally 3 times per day in both the 1-day and 7-day treatment groups, some biochemical and histopathological parameters were significantly altered, both in the ethanol group and the groups receiving ethanol supplemented with CCl(4). A. lappa significantly improved various pathological and biochemical parameters which were worsened by ethanol plus CCl(4)-induced liver damage, such as the ethanol plus CCl(4)-induced decreases in total cytochrome P-450 content and NADPH-cytochrome c reductase activity, increases in serum triglyceride levels and lipid peroxidation (the deleterious peroxidative and toxic malondialdehyde metabolite may be produced in quantity) and elevation of serum transaminase levels. It could even restore the glutathione content and affect the histopathological lesions. These results tended to imply that the hepatotoxicity induced by ethanol and potentiated by CCl(4) could be alleviated with 1 and 7 days of A. lappa treatment. The hepatoprotective mechanism of A. lappa could be attributed, at least in part, to its antioxidative activity, which decreases the oxidative stress of hepatocytes, or to other unknown protective mechanism(s). 相似文献
989.
Krämer SD Hurley JA Abbott NJ Begley DJ 《In vitro cellular & developmental biology. Animal》2002,38(10):557-565
The objectives of this study were to optimize a sensitive high-performance liquid chromatography (HPLC) method for fatty acid (FA) analysis for the quantification of polyunsaturated FAs (PUFAs) in cell lipid extracts and to analyze the lipid and FA patterns of three cell lines used in blood-brain barrier (BBB) models: RBE4, ECV304, and C6. Thin-layer chromatographic analysis revealed differences in the phosphatidylcholine-phosphatidylethanolamine (PC:PE) ratios and the triglyceride (TG) content. The PC:PE ratio was <1 for RBE4 cells but >1 for ECV304 and C6 cells. ECV304 cells displayed up to 9% TG depending on culture time, whereas the other cell lines contained about 1% TG. The percentages of docosahexaenoic acid were 9.4 +/- 1.7% of the unsaturated FAs in RBE4 cells (n = 5; 4 d in culture; 9.9% after 10 d), 8.1 +/- 2.0% in ECV304 cells (n = 11; 10 to 14 d), and 6.7 +/- 0.6% in C6 cells (n = 6; 10 to 14 d) and were close to the published values for rat brain microvascular endothelium. The percentage of arachidonic acid (C20:4) was about half that in vivo. ECV304 cells contained the highest fraction of C20:4, 17.8 +/- 2.2%; RBE4 cells contained 11.6 +/- 2.4%; and C6 cells 15.8 +/- 1.9%. It is concluded that a sensitive HPLC method for FAs is now optimized for the analysis of long-chain PUFAs. The results provide a useful framework for studies on the effects of lipid modulation and give reference information for the development of further BBB models. 相似文献
990.
Beal MF 《Free radical research》2002,36(4):455-460
Coenzyme Q 10 (CoQ 10 ) is an essential cofactor of the electron transport gene as well as an important antioxidant, which is particularly effective within mitochondria. A number of prior studies have shown that it can exert efficacy in treating patients with known mitochondrial disorders. We investigated the potential usefulness of coenzyme Q 10 in animal models of Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD). It has been demonstrated that CoQ 10 can protect against striatal lesions produced by the mitochondrial toxins malonate and 3-nitropropionic acid. These toxins have been utilized to model the striatal pathology, which occurs in HD. It also protects against 1-methyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity in mice. CoQ 10 significantly extended survival in a transgenic mouse model of ALS. CoQ 10 can significantly extend survival, delay motor deficits and delay weight loss and attenuate the development of striatal atrophy in a transgenic mouse model of HD. In this mouse model, it showed additive efficacy when combined with the N -methyl- d -aspartate (NMDA) receptor antagonist, remacemide. CoQ 10 is presently being studied as a potential treatment for early PD as well as in combination with remacemide as a potential treatment for HD. 相似文献