全文获取类型
收费全文 | 1471篇 |
免费 | 83篇 |
国内免费 | 2篇 |
出版年
2022年 | 13篇 |
2021年 | 17篇 |
2020年 | 11篇 |
2019年 | 13篇 |
2018年 | 17篇 |
2017年 | 26篇 |
2016年 | 46篇 |
2015年 | 73篇 |
2014年 | 59篇 |
2013年 | 93篇 |
2012年 | 112篇 |
2011年 | 121篇 |
2010年 | 78篇 |
2009年 | 84篇 |
2008年 | 97篇 |
2007年 | 96篇 |
2006年 | 76篇 |
2005年 | 71篇 |
2004年 | 74篇 |
2003年 | 61篇 |
2002年 | 50篇 |
2001年 | 39篇 |
2000年 | 47篇 |
1999年 | 27篇 |
1998年 | 15篇 |
1997年 | 12篇 |
1996年 | 10篇 |
1995年 | 5篇 |
1994年 | 6篇 |
1993年 | 2篇 |
1992年 | 9篇 |
1991年 | 11篇 |
1990年 | 6篇 |
1989年 | 10篇 |
1988年 | 8篇 |
1987年 | 11篇 |
1986年 | 6篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 5篇 |
1980年 | 3篇 |
1979年 | 4篇 |
1978年 | 5篇 |
1977年 | 3篇 |
1976年 | 4篇 |
1974年 | 2篇 |
1971年 | 2篇 |
1968年 | 1篇 |
排序方式: 共有1556条查询结果,搜索用时 156 毫秒
101.
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
102.
Choong Hyun Lee Ki-Yeon Yoo Ok Kyu Park Jung Hoon Choi Il-Jun Kang Eunjoo Bae Sung Koo Kim In Koo Hwang Moo-Ho Won 《Molecules and cells》2010,29(4):373-378
Phosphorylated extracellular signal-regulated kinase (pERK) mediates neuronal synaptic plasticity, long-term potentiation,
and learning and memory in the hippocampus. In this study, we examined pERK1/2 immunoreactivity and its protein level in the
gerbil hippocampus at various ages. In the postnatal month 1 (PM 1) group, very weak pERK1/2 immunoreactivity was detected
in the hippocampus. In the CA1 region, pERK1/2 immunoreactivity was considerably increased in the stratum pyramidale in the
PM 6 group. Thereafter, pERK1/2 immunoreactivity was decreased. In the CA2/3 region, pERK1/2 immunoreactivity increased in
an age-dependent manner until PM 12. Thereafter, numbers of pERK1/2-immunoreactive neurons were decreased. However, in the
mossy fiber zone, pERK1/2 immunostaining became stronger with age. In the dentate gyrus, a few pERK1/2-immunoreactive cells
were observed until PM 12. In the PM 18 and 24 groups, numbers of pERK1/2-immunoreactive cells were increased, especially
in the polymorphic layer. In Western blot analysis, pERK1/2 level in the gerbil hippocampus was increased with age. These
results indicate that total pERK1/2 levels are increased in the hippocampus with age. However pERK1/2 immunoreactivity in
subregions of the gerbil hippocampus was changed with different pattern during normal aging. 相似文献
103.
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
104.
Autotrophic and heterotrophic respiration in needle fir and Quercus-dominated stands in a cool-temperate forest, central Korea 总被引:3,自引:0,他引:3
Na-yeon Lee Jin-Woo Koo Nam Jin Noh Joon Kim Yowhan Son 《Journal of plant research》2010,123(4):485-495
To investigate annual variation in soil respiration (R
S) and its components [autotrophic (R
A) and heterotrophic (R
H)] in relation to seasonal changes in soil temperature (ST) and soil water content (SWC) in an Abies holophylla stand (stand A) and a Quercus-dominated stand (stand Q), we set up trenched plots and measured R
S, ST and SWC for 2 years. The mean annual rate of R
S was 436 mg CO2 m−2 h−1, ranging from 76 to 1,170 mg CO2 m−2 h−1, in stand A and 376 mg CO2 m−2 h−1, ranging from 82 to 1,133 mg CO2 m−2 h−1, in stand Q. A significant relationship between R
S and its components and ST was observed over the 2 years in both stands, whereas a significant correlation between R
A and SWC was detected only in stand Q. On average over the 2 years, R
A accounted for approximately 34% (range 17–67%) and 31% (15–82%) of the variation in R
S in stands A and Q, respectively. Our results suggested that vegetation type did not significantly affect the annual mean
contributions of R
A or R
H, but did affect the pattern of seasonal change in the contribution of R
A to R
S. 相似文献
105.
106.
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
107.
Cecilie?M?MejdellEmail author Grete?HM?J?rgensen Therese?Rehn Kjersti?Fremstad Linda?Keeling Knut?E?B?e 《Acta veterinaria Scandinavica》2010,52(1):68
Background
The risk of injuries is of major concern when keeping horses in groups and there is a need for a system to record external injuries in a standardised and simple way. The objective of this study, therefore, was to develop and validate a system for injury recording in horses and to test its reliability and feasibility under field conditions.Methods
Injuries were classified into five categories according to severity. The scoring system was tested for intra- and inter-observer agreement as well as agreement with a 'golden standard' (diagnosis established by a veterinarian). The scoring was done by 43 agricultural students who classified 40 photographs presented to them twice in a random order, 10 days apart. Attribute agreement analysis was performed using Kendall's coefficient of concordance (Kendall's W), Kendall's correlation coefficient (Kendall's τ) and Fleiss' kappa. The system was also tested on a sample of 100 horses kept in groups where injury location was recorded as well.Results
Intra-observer agreement showed Kendall's W ranging from 0.94 to 0.99 and 86% of observers had kappa values above 0.66 (substantial agreement). Inter-observer agreement had an overall Kendall's W of 0.91 and the mean kappa value was 0.59 (moderate). Agreement for all observers versus the 'golden standard' had Kendall's τ of 0.88 and the mean kappa value was 0.66 (substantial). The system was easy to use for trained persons under field conditions. Injuries of the more serious categories were not found in the field trial.Conclusion
The proposed injury scoring system is easy to learn and use also for people without a veterinary education, it shows high reliability, and it is clinically useful. The injury scoring system could be a valuable tool in future clinical and epidemiological studies.108.
Background
Apoptosis is an essential cell death process throughout the entire life span of all metazoans and its deregulation in humans has been implicated in many proliferative and degenerative diseases. Mitochondrial outer membrane permeabilisation (MOMP) and activation of effector caspases are key processes during apoptosis signalling. MOMP can be subject to spatial coordination in human cancer cells, resulting in intracellular waves of cytochrome-c release. To investigate the consequences of these spatial anisotropies in mitochondrial permeabilisation on subsequent effector caspase activation, we devised a mathematical reaction-diffusion model building on a set of partial differential equations. 相似文献109.
Jessica AB van Nies Rute B Marques Stella Trompet Zuzana de Jong Fina AS Kurreeman Rene EM Toes J Wouter Jukema Tom WJ Huizinga Annette HM van der Helm-van Mil 《Arthritis research & therapy》2010,12(2):R38
Introduction
Recently an association between a genetic variation in TRAF1/C5 and mortality from sepsis or cancer was found in rheumatoid arthritis (RA). The most prevalent cause of death, cardiovascular disease, may have been missed in that study, since patients were enrolled at an advanced disease stage. Therefore, we used an inception cohort of RA patients to investigate the association between TRAF1/C5 and cardiovascular mortality, and replicate the findings on all-cause mortality. As TRAF1/C5 associated mortality may not be restricted to RA, we also studied a large cohort of non-RA patients. 相似文献110.
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