首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   14247篇
  免费   1360篇
  国内免费   2228篇
  17835篇
  2024年   63篇
  2023年   263篇
  2022年   639篇
  2021年   930篇
  2020年   729篇
  2019年   842篇
  2018年   713篇
  2017年   562篇
  2016年   719篇
  2015年   1042篇
  2014年   1272篇
  2013年   1262篇
  2012年   1559篇
  2011年   1488篇
  2010年   894篇
  2009年   756篇
  2008年   833篇
  2007年   699篇
  2006年   571篇
  2005年   432篇
  2004年   318篇
  2003年   284篇
  2002年   205篇
  2001年   94篇
  2000年   100篇
  1999年   103篇
  1998年   77篇
  1997年   60篇
  1996年   53篇
  1995年   43篇
  1994年   39篇
  1993年   25篇
  1992年   31篇
  1991年   33篇
  1990年   22篇
  1989年   16篇
  1988年   12篇
  1987年   7篇
  1986年   3篇
  1985年   19篇
  1984年   5篇
  1983年   2篇
  1982年   4篇
  1981年   2篇
  1978年   2篇
  1975年   1篇
  1973年   1篇
  1972年   1篇
  1965年   1篇
  1938年   1篇
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
髓鞘碱性蛋白(myelin basic protein,MBP)是中枢神经系统(central nervous system,CNS)髓鞘成熟期的主要蛋白质之一.研究资料表明,MBP与变态反应性脑脊髓炎(allergic encephalomyelitis,EAE)、多发性硬化等多种神经疾病有关,是反映中枢神经系统有无...  相似文献   
992.

Background

A number of studies evaluated the association of intracellular adhesion molecule-1 (ICAM-1) K469E (rs5498, A/G) gene polymorphism with diabetic microvascular complications (DMI) including diabetic nephropathy (DN) and diabetic retinopathy (DR) in different populations. However, the results of individual studies remain conflicting.

Methods

A comprehensive search was conducted to identify all eligible studies of the above-mentioned associations. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were assessed using the fixed or random effect model.

Results

Seven studies involving 3411 subjects were included. Overall, the meta-analysis showed a significant association of the A allele with increased risk of DMI susceptibility in a recessive model (OR = 1.37, 95% CI 1.04–1.80, P = 0.02). In the subgroup analysis stratified by ethnicity, significant association was found in Asians but not in Caucasians (OR = 1.78, 95% CI 1.13–2.81, P = 0.01; OR = 1.10, 95% CI 0.79–1.54, P = 0.58, respectively). Moreover, it showed a significant association between the A allele and risk of DN in a recessive model (OR = 1.25, 95% CI 1.02–1.55, P = 0.04).

Conclusions

This meta-analysis suggested that the K469E polymorphism in ICAM-1 gene might affect individual susceptibility to DMI and showed a discrepancy in different ethnicities. Further investigations are needed to validate the association.  相似文献   
993.
994.

Purpose

This study was intended to identify the disease causing genes in a large Chinese family with autosomal dominant retinitis pigmentosa and macular degeneration.

Methods

A genome scan analysis was conducted in this family for disease gene preliminary mapping. Snapshot analysis of selected SNPs for two-point LOD score analysis for candidate gene filter. Candidate gene PRPF31 whole exons'' sequencing was executed to identify mutations.

Results

A novel nonsense mutation caused by an insertion was found in PRPF31 gene. All the 19 RP patients in 1085 family are carrying this heterozygous nonsense mutation. The nonsense mutation is in PRPF31 gene exon9 at chr19:54629961-54629961, inserting nucleotide “A” that generates the coding protein frame shift from p.307 and early termination at p.322 in the snoRNA binding domain (NOP domain).

Conclusion

This report is the first to associate PRPF31 gene''s nonsense mutation and adRP and JMD. Our findings revealed that PRPF31 can lead to different clinical phenotypes in the same family, resulting either in adRP or syndrome of adRP and JMD. We believe our identification of the novel “A” insertion mutation in exon9 at chr19:54629961-54629961 in PRPF31 can provide further genetic evidence for clinical test for adRP and JMD.  相似文献   
995.
&#  &#  &#  &#  &#  &#  &#  &#  &#  &#  &#  &#  &#  &#  &#  &#  &#  &#  &#  &#  &#  &# 《水生生物学报》2013,37(4):766-771
鲟隶属于鲟形目(Acipenseriformes), 是中国近年来养殖发展较快的淡水养殖品种。虽然养殖技术及条件要求较高, 但是由于养殖鲟鱼具有很高的经济价值, 而且生长快、肉质好、全身是宝, 因而受到广大养殖户推崇1。但是近年来随着养殖量的迅速增大, 养殖集约化程度不断提高, 造成鲟养殖环境不断恶化, 使得鲟体质普遍下降, 发病率大增。鲟鱼多发细菌性疾病, 暴发性强, 死亡率高, 主要病原菌包括链球菌等革兰氏阳性菌和气单胞菌属几种27, 因此疾病逐渐成为鲟鱼健康养殖的一大障碍。    相似文献   
996.
997.
目的:为帮助医师在口腔诊疗过程中拍摄出更有说服力的图片,更好的在口腔诊疗过程中与就诊的患者进行良好的沟通,本文就摄影中最重要的光圈值的设定进行系统的研究评价,希望可以获得适合口腔临床使用的光圈值的设定.方法:运用单盲法对各个光圈值拍摄的图片进行比对,主观上选出让口腔临床医师比较满意的口内摄影图片,并对最具有代表性的图片列表比较.结果:光圈值为F32的口腔数码摄影图片与其他光圈值所得的图片相比较,光圈值为F32的口内图片反映口腔内细节效果最佳.结论:在相同设置的条件下,临床上进行口腔内摄影时,选择光圈值F32可以非常好的满足口腔临床医生对口内细节的表现,达到所需的临床效果,临床上最适合口腔数码摄影.  相似文献   
998.
Extramedullary hematopoiesis has been shown to contribute to the pathogenesis of a variety of diseases including cardiovascular diseases. In this process, the spleen is seeded with mobilized bone marrow cells that augment its hematopoietic ability. It is unclear whether these immigrant cells that are produced/reprogrammed in spleen are similar or different from those found in the bone marrow. To begin to understand this, we investigated the relative potency of adult splenocytes per se to repopulate bone marrow of lethally-irradiated mice and its functional consequences in atherosclerosis. The splenocytes were harvested from GFP donor mice and transplanted into myeloablated wild type recipient mice without the inclusion of any bone marrow helper cells. We found that adult splenocytes repopulated bone marrow of myeloablated mice and the transplanted cells differentiated into a full repertoire of myeloid cell lineages. The level of monocytes/macrophages in the bone marrow of recipient mice was dependent on the cell origin, i.e., the donor splenocytes gave rise to significantly more monocytes/macrophages than the donor bone marrow cells. This occurred despite a significantly lower number of hematopoietic stem cells being present in the donor splenocytes when compared with donor bone marrow cells. Atherosclerosis studies revealed that donor splenocytes displayed a similar level of atherogenic and atheroprotective activities to those of donor bone marrow cells. Cell culture studies showed that the phenotype of macrophages derived from spleen is different from those of bone marrow. Together, these results demonstrate that splenocytes can seed bone marrow of myeloablated mice and modulate atherosclerosis. In addition, our study shows the potential of splenocytes for therapeutic interventions in inflammatory disease.  相似文献   
999.
Jain P  Sun L  Dai J  Baker GL  Bruening ML 《Biomacromolecules》2007,8(10):3102-3107
Porous membrane absorbers are attractive for increasing the rate of protein purification, but their binding capacity is low relative to porous beads. Modification of membranes with functionalized polymer brushes, however, can greatly enhance capacity. This work demonstrates that membrane modification with poly(2-hydroxyethyl methacrylate) (PHEMA) brushes derivatized with nitrilotriacetate-Ni2+ (NTA-Ni2+) complexes allows purification of polyhistidine-tagged ubiquitin (HisU) in less than 30 min with a binding capacity of 120 mg of HisU/cm3 of porous alumina membrane. Adsorption isotherms show that saturation of the brushes occurs at HisU concentrations as low as 0.04 mg/mL and that these brushes can bind up to 23 monolayers of HisU. Gel electrophoresis reveals that the purity of eluted HisU is more than 99%, even when the initial feed solution contains 10% bovine serum or a 20-fold excess of BSA. Thus, reusable porous membranes modified by PHEMA-NTA-Ni2+ brushes are attractive candidates for rapid purification of polyhistidine-tagged proteins.  相似文献   
1000.
To investigate the evolution and immune function of C-type lectin in amphioxus, the primitive representative of the chordate phylum, we identified three C-type lectins consisting solely of a carbohydrate recognition domain and N-terminal signal peptide and found that they had distinct express patterns in special tissues and immune response to stimulations analyzed by quantitative real-time PCR. We characterized the biochemical and biological properties of AmphiCTL1, which was dramatically up-regulated in amphioxus challenged with Staphylococcus aureus, Saccharomyces cerevisiae, and zymosan. Immunohistochemistry demonstrated that the localization of AmphiCTL1 protein was exclusively detected in the inner folding tissues of the hepatic diverticulum. Recombinant AmphiCTL1 was characterized as a typical Ca2+-dependent carbohydrate-binding protein possessing hemagglutinating activity, preferentially bound to all examined four Gram-positive bacteria and two yeast strains, but had little binding activity toward four Gram-negative bacteria we tested. It aggregated S. aureus and S. cerevisiae in a Ca2+-dependent manner and specifically bound to insoluble peptidoglycan and glucan, but not to LPS, lipoteichoic acid, and mannan. Calcium increased the intensity of the interaction between AmphiCTL1 and those components, but was not essential. This lectin directly killed S. aureus and S. cerevisiae in a Ca2+-independent fashion, and its binding to microorganism cell wall polysaccharides such as peptidoglycan and glucan preceded microbial killing activity. These findings suggested that AmphiCTL1 acted as a direct microbial killing C-type lectin through binding microbial targets via interaction with peptidoglycan and glucan. Thus, AmphiCTL1 may be an evolutionarily primitive form of antimicrobial protein involved in lectin-mediated innate immunity.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号