全文获取类型
收费全文 | 1386篇 |
免费 | 81篇 |
国内免费 | 3篇 |
专业分类
1470篇 |
出版年
2022年 | 13篇 |
2021年 | 17篇 |
2020年 | 11篇 |
2019年 | 14篇 |
2018年 | 18篇 |
2017年 | 25篇 |
2016年 | 44篇 |
2015年 | 68篇 |
2014年 | 51篇 |
2013年 | 87篇 |
2012年 | 112篇 |
2011年 | 112篇 |
2010年 | 67篇 |
2009年 | 76篇 |
2008年 | 90篇 |
2007年 | 93篇 |
2006年 | 73篇 |
2005年 | 69篇 |
2004年 | 71篇 |
2003年 | 60篇 |
2002年 | 49篇 |
2001年 | 38篇 |
2000年 | 43篇 |
1999年 | 25篇 |
1998年 | 14篇 |
1997年 | 10篇 |
1996年 | 9篇 |
1995年 | 4篇 |
1994年 | 6篇 |
1992年 | 9篇 |
1991年 | 10篇 |
1990年 | 6篇 |
1989年 | 9篇 |
1988年 | 8篇 |
1987年 | 11篇 |
1986年 | 6篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1981年 | 5篇 |
1980年 | 3篇 |
1979年 | 4篇 |
1978年 | 4篇 |
1977年 | 3篇 |
1976年 | 4篇 |
1974年 | 2篇 |
1972年 | 1篇 |
1971年 | 2篇 |
1969年 | 1篇 |
1968年 | 1篇 |
排序方式: 共有1470条查询结果,搜索用时 15 毫秒
111.
The chemical synthesis and incorporation of the phosphoramidite derivatives of 2?′-O-photocaged ribonucleosides (A, C, G and U) with o-nitrobenzyl, α-methyl-o-nitrobenzyl or 4,5-dimethoxy-2-nitrobenzyl group into oligoribonucleotides are described. The efficiency of UV irradiated uncaging of these 2′-O-photocaged oligoribonucleotides was found in the order of α-methyl-o-nitrobenzyl < 4,5-dimethoxy-2-nitrobenzyl < 2′-O-o-nitrobenzyl. 相似文献
112.
113.
Objective
To understand and predict chronic obstructive pulmonary disease (COPD), a biomarker that reflects disease severity is needed.Research Design and Methods
Data from 10269 adults aged over 40 years of age were retrieved from the Korea National Health and Nutrition Examination Survey (KNHANES), and 1302 patients met the criteria for COPD. The association between values of vitamin D and parathyroid hormone (PTH), and COPD severity including lung function and quality of life, were analyzed.Results
In COPD patients, lung function was inversely related to PTH values (P = 0.02 for FVC [% predicted]; P < 0.001 for FEV1 [% predicted]); however, the association of lung function with vitamin D levels was not statistically significant in a multivariable analysis. Value of PTH was independently associated with EQ5D-index (P = 0.04), but vitamin D level showed no significant relationship with EQ5D-index (P = 0.59) or EQ5D-VAS (P = 0.81).Conclusions
Elevation of PTH, unlike vitamin D, is independently associated with COPD severity, and may be a better biomarker for COPD. 相似文献114.
Sumei Liao Marlise I. Klein Kyle P. Heim Yuwei Fan Jacob P. Bitoun San-Joon Ahn Robert A. Burne Hyun Koo L. Jeannine Brady Zezhang T. Wen 《Journal of bacteriology》2014,196(13):2355-2366
Streptococcus mutans, a major etiological agent of human dental caries, lives primarily on the tooth surface in biofilms. Limited information is available concerning the extracellular DNA (eDNA) as a scaffolding matrix in S. mutans biofilms. This study demonstrates that S. mutans produces eDNA by multiple avenues, including lysis-independent membrane vesicles. Unlike eDNAs from cell lysis that were abundant and mainly concentrated around broken cells or cell debris with floating open ends, eDNAs produced via the lysis-independent pathway appeared scattered but in a structured network under scanning electron microscopy. Compared to eDNA production of planktonic cultures, eDNA production in 5- and 24-h biofilms was increased by >3- and >1.6-fold, respectively. The addition of DNase I to growth medium significantly reduced biofilm formation. In an in vitro adherence assay, added chromosomal DNA alone had a limited effect on S. mutans adherence to saliva-coated hydroxylapatite beads, but in conjunction with glucans synthesized using purified glucosyltransferase B, the adherence was significantly enhanced. Deletion of sortase A, the transpeptidase that covalently couples multiple surface-associated proteins to the cell wall peptidoglycan, significantly reduced eDNA in both planktonic and biofilm cultures. Sortase A deficiency did not have a significant effect on membrane vesicle production; however, the protein profile of the mutant membrane vesicles was significantly altered, including reduction of adhesin P1 and glucan-binding proteins B and C. Relative to the wild type, deficiency of protein secretion and membrane protein insertion machinery components, including Ffh, YidC1, and YidC2, also caused significant reductions in eDNA. 相似文献
115.
Choong Hyun Lee Jung Hoon Choi Ki-Yeon Yoo Ok Kyu Park In Koo Hwang Sang Guan You Boo-Yong Lee Il-Jun Kang Moo-Ho Won 《Cellular and molecular neurobiology》2010,30(2):255-263
Melatonin exerts many physiological functions via its G protein-coupled receptors. In the present study, we investigated age-related
changes in MT2 melatonin receptor immunoreactivity and its levels in the gerbil hippocampus during normal aging. In the postnatal
month 1 (PM 1) group, MT2 immunoreaction was well observed in neurons in all subregions of the gerbil hippocampus. In the
PM 3 and 6 groups, MT2 immunoreactivity in neurons was decreased compared to that in the PM 1 group. Thereafter, MT2 immunoreactivity
in neurons was increased. In the PM 18 and 24 groups, MT2 immunoreactivity in neurons was strong in all subregions of the
gerbil hippocampus. In addition, the number of MT2 immunoreactive cells was lowest at PM 3 and highest at PM 24. From western
blot analysis, age-dependent change pattern in MT2 level in the gerbil hippocampus was similar to the immunohistochemical
result. These results indicate that MT2 immunoreactivity and levels are altered in the gerbil hippocampus during normal aging;
lowest at young adult stage and highest at aged stage. 相似文献
116.
Dae Won Chung Ki-Yeon Yoo In Koo Hwang Dae Won Kim Jin Young Chung Choong Hyun Lee Jung Hoon Choi Soo Young Choi Hwa Young Youn In Se Lee Moo-Ho Won 《Cellular and molecular neurobiology》2010,30(4):531-541
In this study, we observed the effects of lipopolysaccharide (LPS) on neurodegeneration and immune response in the hippocampus. LPS is a gram-negative bacterial cell surface proteoglycan and known as a bacterial endotoxin. For this, we investigated the optimal concentration of LPS influencing the ICR mouse hippocampus to measure the LPS receptor, e.g., toll-like receptor 4 (TLR4), expression in mouse hippocampal homogenates. TLR4 expression was significantly and prominently increased in the hippocampal homogenates of the LPS (1 mg/kg)-treated group. Next, we examined pro-inflammatory response in the hippocampus using cyclooxygenase-2 (COX-2, a marker for inflammatory response) immunohistochemistry after LPS treatment. COX-2 immunoreactivity was significantly increased in the endothelium of blood vessels in the hippocampus 6 h after LPS treatment, judging from double immunofluorescence study with platelet-derived endothelial cell adhesion molecule-1 (PECAM-1, a marker for endothelial cells): it decreased 12 h and disappeared 24 h after LPS treatment. In addition, the ionized calcium-binding adapter molecule 1 (Iba-1)-immunoreactive (+) microglia were morphologically activated in the mouse hippocampus after LPS treatment. At 24 h after LPS treatment, Iba-1+ microglia of activated forms were abundant in the hippocampus. However, NeuN (a neuron-specific soluble nuclear antigen)+ neurons were not significantly changed in the hippocampus after LPS treatment. Fluoro-jade B (a marker for neuronal degeneration)+ cells were not detected in the hippocampus at any time after LPS treatment. In addition, there were no significant differences in permeability of blood–brain barriers at any time points after LPS treatment. In brief, our results indicate that intraperitoneal administration of 1 mg/kg LPS effectively induces LPS receptor (TLR4) expression in the hippocampus, and the treatment increases corticosterone levels, inflammation in the blood vessels, and microglial activation in the hippocampus without any neuronal damage. 相似文献
117.
Yi DK Sun IC Ryu JH Koo H Park CW Youn IC Choi K Kwon IC Kim K Ahn CH 《Bioconjugate chemistry》2010,21(12):2173-2177
Herein, we developed matrix metalloprotease (MMP) sensitive gold nanorods (MMP-AuNR) for cancer imaging and therapy. It was feasible to absorb NIR laser and convert into heat as well as visualize MMP activity. We showed the possibility of gold nanorods as a hyperthermal therapeutic agent and MMP sensitive imaging agent both in vitro and in vivo condition. The results suggested potential application of MMP-AuNR for simultaneous cancer diagnosis and therapy. 相似文献
118.
Fanconi anemia (FA) patients are specifically defective in the repair of interstrand DNA crosslinks (ICLs), a complex process involving at least 13 FA proteins and other repair/checkpoint proteins. Of the 13 FA proteins, FANCD1/BRCA2, FANCD2, and FANCJ were previously found to be functionally conserved in C. elegans. We have also identified C. elegans homologs of FANCM and FANCI, and determined their epistatic relationships with homologs of FANCD2, checkpoint proteins, and RAD51 upon DNA crosslinking. The counterparts of FANCM, FANCI, and three checkpoint proteins (RPA, ATR and CHK1) are required for focus formation and ubiquitination associated with FANCD2 in C. elegans. However, C. elegans FANCM affects neither RPA focus formation nor CHK1 phosphorylation induced by ICLs, unlike the reported role of human FANCM, which influences ATR-CHK1 signaling at stalled replication forks. Although focus formation by both FANCD2 and RAD51 requires ATR-CHK1 signaling, FANCD2 and RAD51 acted independently in the formation of their respective foci. Thus, the FANCD2 activation pathway involving FANCM, FANCI, and the checkpoint proteins is conserved in C. elegans but with distinct differences. 相似文献
119.
Cartilage contact geometry, along with joint loading, can play an important role in determining local articular cartilage tissue stress. Thus individual variations in cartilage thickness can be associated with both individual variations in joint loading associated with activities of daily living as well as individual differences in the anatomy of the contacting surfaces of the joint. The purpose of this study was to isolate the relationship between cartilage thickness predicted by individual variations in contact surface geometry based on the radii of the femur and tibia vs. cartilage thickness predicted by individual variations in joint loading. Knee magnetic resonance (MR) images and the peak knee adduction moments during walking were obtained from 11 young healthy male subjects (age 30.5+/-5.1 years). The cartilage thicknesses and surface radii of the femoral and tibial cartilage were measured in the weight-bearing regions of the medial and lateral compartments of three-dimensional models from the MR images. The ratio of contact pressure between the medial and lateral compartments was calculated from the radii of tibiofemoral contact surface geometries. The results showed that the medial to lateral pressure ratios were not correlated with the medial to lateral cartilage thickness ratios. However, in general, pressure was higher in the lateral than medial compartments and cartilage was thicker in the lateral than medial compartments. The peak knee adduction moment showed a significant positive linear correlation with medial to lateral thickness ratio in both femur (R(2)=0.43,P<0.01) and tibia (R(2)=0.32,P<0.01). The results of this study suggest that the dynamics of walking is an important factor to describe individual differences in cartilage thickness for normal subjects. 相似文献
120.
The gastric mucosa is frequently exposed to different exogenous and endogenous ulcerative agents. Alcoholism is one of the risk factors for the development of mucosal damage in the stomach. This study aimed to assess if a probiotic strain Lactobacillus rhamnosus GG (LGG) is capable of protecting the gastric mucosa from acute damage induced by intragastric administration of ethanol. Pre-treatment of rats with LGG at 10(9) cfu/ml twice daily for three consecutive days markedly reduced ethanol-induced mucosal lesion area by 45%. LGG pre-treatment also significantly increased the basal mucosal prostaglandin E(2) (PGE(2)) level. In addition, LGG attenuated the suppressive actions of ethanol on mucus-secreting layer and transmucosal resistance and reduced cellular apoptosis in the gastric mucosa. It is suggested that the protective action of LGG on ethanol-induced gastric mucosal lesions is likely attributed to the up-regulation of PGE(2), which could stimulate the mucus secretion and increase the transmucosal resistance in the gastric mucosa. All these would protect mucosal cells from apoptosis in the stomach. 相似文献