全文获取类型
收费全文 | 3870篇 |
免费 | 324篇 |
国内免费 | 610篇 |
出版年
2024年 | 16篇 |
2023年 | 97篇 |
2022年 | 198篇 |
2021年 | 368篇 |
2020年 | 266篇 |
2019年 | 266篇 |
2018年 | 250篇 |
2017年 | 181篇 |
2016年 | 219篇 |
2015年 | 340篇 |
2014年 | 350篇 |
2013年 | 365篇 |
2012年 | 416篇 |
2011年 | 312篇 |
2010年 | 167篇 |
2009年 | 163篇 |
2008年 | 167篇 |
2007年 | 121篇 |
2006年 | 99篇 |
2005年 | 73篇 |
2004年 | 40篇 |
2003年 | 51篇 |
2002年 | 41篇 |
2001年 | 25篇 |
2000年 | 28篇 |
1999年 | 22篇 |
1998年 | 17篇 |
1997年 | 21篇 |
1996年 | 22篇 |
1995年 | 8篇 |
1994年 | 14篇 |
1993年 | 3篇 |
1992年 | 12篇 |
1991年 | 16篇 |
1990年 | 12篇 |
1989年 | 10篇 |
1988年 | 9篇 |
1987年 | 3篇 |
1986年 | 8篇 |
1985年 | 3篇 |
1984年 | 1篇 |
1983年 | 3篇 |
1982年 | 1篇 |
排序方式: 共有4804条查询结果,搜索用时 15 毫秒
91.
Peng Liu Wei Qin Jingjing Wang Fang Zeng Guangyu Zhou Haixia Wen Karen M. von Deneen Fanrong Liang Qiyong Gong Jie Tian 《PloS one》2013,8(7)
Background
Previous imaging studies on functional dyspepsia (FD) have focused on abnormal brain functions during special tasks, while few studies concentrated on the resting-state abnormalities of FD patients, which might be potentially valuable to provide us with direct information about the neural basis of FD. The main purpose of the current study was thereby to characterize the distinct patterns of resting-state function between FD patients and healthy controls (HCs).Methodology/Principal Findings
Thirty FD patients and thirty HCs were enrolled and experienced 5-mintue resting-state scanning. Based on the support vector machine (SVM), we applied multivariate pattern analysis (MVPA) to investigate the differences of resting-state function mapped by regional homogeneity (ReHo). A classifier was designed by using the principal component analysis and the linear SVM. Permutation test was then employed to identify the significant contribution to the final discrimination. The results displayed that the mean classifier accuracy was 86.67%, and highly discriminative brain regions mainly included the prefrontal cortex (PFC), orbitofrontal cortex (OFC), supplementary motor area (SMA), temporal pole (TP), insula, anterior/middle cingulate cortex (ACC/MCC), thalamus, hippocampus (HIPP)/parahippocamus (ParaHIPP) and cerebellum. Correlation analysis revealed significant correlations between ReHo values in certain regions of interest (ROI) and the FD symptom severity and/or duration, including the positive correlations between the dmPFC, pACC and the symptom severity; whereas, the positive correlations between the MCC, OFC, insula, TP and FD duration.Conclusions
These findings indicated that significantly distinct patterns existed between FD patients and HCs during the resting-state, which could expand our understanding of the neural basis of FD. Meanwhile, our results possibly showed potential feasibility of functional magnetic resonance imaging diagnostic assay for FD. 相似文献92.
Both the clinical diagnosis and fundamental investigation of major ocular diseases greatly benefit from various non-invasive ophthalmic imaging technologies. Existing retinal imaging modalities, such as fundus photography1, confocal scanning laser ophthalmoscopy (cSLO)2, and optical coherence tomography (OCT)3, have significant contributions in monitoring disease onsets and progressions, and developing new therapeutic strategies. However, they predominantly rely on the back-reflected photons from the retina. As a consequence, the optical absorption properties of the retina, which are usually strongly associated with retinal pathophysiology status, are inaccessible by the traditional imaging technologies.Photoacoustic ophthalmoscopy (PAOM) is an emerging retinal imaging modality that permits the detection of the optical absorption contrasts in the eye with a high sensitivity4-7 . In PAOM nanosecond laser pulses are delivered through the pupil and scanned across the posterior eye to induce photoacoustic (PA) signals, which are detected by an unfocused ultrasonic transducer attached to the eyelid. Because of the strong optical absorption of hemoglobin and melanin, PAOM is capable of non-invasively imaging the retinal and choroidal vasculatures, and the retinal pigment epithelium (RPE) melanin at high contrasts 6,7. More importantly, based on the well-developed spectroscopic photoacoustic imaging5,8 , PAOM has the potential to map the hemoglobin oxygen saturation in retinal vessels, which can be critical in studying the physiology and pathology of several blinding diseases 9 such as diabetic retinopathy and neovascular age-related macular degeneration.Moreover, being the only existing optical-absorption-based ophthalmic imaging modality, PAOM can be integrated with well-established clinical ophthalmic imaging techniques to achieve more comprehensive anatomic and functional evaluations of the eye based on multiple optical contrasts6,10 . In this work, we integrate PAOM and spectral-domain OCT (SD-OCT) for simultaneously in vivo retinal imaging of rat, where both optical absorption and scattering properties of the retina are revealed. The system configuration, system alignment and imaging acquisition are presented. 相似文献
93.
Recent advances in nanotechnologies have led to wide use of nanomaterials in biomedical field. However, nanoparticles are found to interfere with protein misfolding and aggregation associated with many human diseases. It is still a controversial issue whether nanoparticles inhibit or promote protein aggregation. In this study, we used molecular dynamics simulations to explore the effects of three kinds of carbon nanomaterials including graphene, carbon nanotube and C60 on the aggregation behavior of islet amyloid polypeptide fragment 22–28 (IAPP22–28). The diverse behaviors of IAPP22–28 peptides on the surfaces of carbon nanomaterials were studied. The results suggest these nanomaterials can prevent β-sheet formation in differing degrees and further affect the aggregation of IAPP22–28. The π–π stacking and hydrophobic interactions are different in the interactions between peptides and different nanoparticles. The subtle differences in the interaction are due to the difference in surface curvature and area. The results demonstrate the adsorption interaction has competitive advantages over the interactions between peptides. Therefore, the fibrillation of IAPP22–28 may be inhibited at its early stage by graphene or SWCNT. Our study can not only enhance the understanding about potential effects of nanomaterials to amyloid formation, but also provide valuable information to develop potential β-sheet formation inhibitors against type II diabetes. 相似文献
94.
95.
Xiaoteng Fu Jinzhuang Dou Junxia Mao Hailin Su Wenqian Jiao Lingling Zhang Xiaoli Hu Xiaoting Huang Shi Wang Zhenmin Bao 《PloS one》2013,8(11)
Genetic linkage maps are indispensable tools in genetic, genomic and breeding studies. As one of genotyping-by-sequencing methods, RAD-Seq (restriction-site associated DNA sequencing) has gained particular popularity for construction of high-density linkage maps. Current RAD analytical tools are being predominantly used for typing codominant markers. However, no genotyping algorithm has been developed for dominant markers (resulting from recognition site disruption). Given their abundance in eukaryotic genomes, utilization of dominant markers would greatly diminish the extensive sequencing effort required for large-scale marker development. In this study, we established, for the first time, a novel statistical framework for de novo dominant genotyping in mapping populations. An integrated package called RADtyping was developed by incorporating both de novo codominant and dominant genotyping algorithms. We demonstrated the superb performance of RADtyping in achieving remarkably high genotyping accuracy based on simulated and real mapping datasets. The RADtyping package is freely available at http://www2.ouc.edu.cn/mollusk/ detailen.asp?id=727. 相似文献
96.
Background
Expanded criteria donors (ECDs) are currently accepted as potential sources to increase the donor pool and to provide more chances of kidney transplantation for elderly recipients who would not survive long waiting periods. Hypothermic machine perfusion (HMP) is designed to mitigate the deleterious effects of simple cold storage (CS) on the quality of preserved organs, particularly when the donor is in a marginal status.Methods
We compared the transplant outcomes in patients receiving ECD kidneys with either HMP or CS graft preservation. Articles from the MEDLINE, EMBASE and Cochrane Library databases were searched and all studies reporting outcomes from HMP versus CS methods of kidney preservation were included in this meta-analysis. The parameters analyzed included the incidence of delayed graft function (DGF), primary non-function (PNF) and one-year graft and patient survival.Results
A total of seven studies qualified for the review, involving 2374 and 8716 kidney grafts with HMP or CS preservation respectively, all from ECD donors. The incidence of delayed graft function (DGF) was significantly reduced with an odd ratio(OR) of 0.59 (95% CI 0.54–0.66, P<0.001) and one-year graft survival was significantly improved with an OR of 1.12 (95% CI 1.03–1.21, P = 0.005) in HMP preservation compared to CS. However, there was no difference in the incidence of PNF (OR 0.54, 95% CI 0.21–1.40, P = 0.20), and one-year patient survival (OR 0.98, 95% CI 0.94–1.02, P = 0.36) between HMP and CS preservation.Conclusions
HMP was associated with a reduced incidence of DGF and an with increased one-year graft survival, but it was not associated with the incidence of PNF and one-year patient survival. 相似文献97.
Weiwei Jiao Zhiguang Liu Rui Han Xiuqin Zhao Fang Dong Haiyan Dong Hairong Huang Jianling Tian Qinjing Li Lulu Lian Qingqin Yin Wenqi Song Kanglin Wan A-dong Shen 《PloS one》2013,8(12)
Background
Tuberculosis (TB) is still a big threat to human health, especially in children. However, an isolation of Mycobacterium tuberculosis culture from pediatric cases remains a challenge. In order to provide some scientific basis for children TB control, we investigated the genotyping and drug resistance characteristics of M. tuberculosis isolates from pediatric cases in China.Methodology/Principal Findings
In this study, a total of 440 strains including 90 from children (<15 years), 159 from adolescents (15–18 years) and 191 from adults (>18 years) isolated in 25 provinces across China were subjected to spoligotyping and drug susceptibility testing. As a result, Beijing family strains were shown to remain predominant in China (85.6%, 81.1% and 75.4% in three above groups, respectively), especially among new children cases (91.0% vs. 69.6% in previously treated cases, P = 0.03). The prevalence of the Beijing genotype isolates was higher in northern and central China in the total collection (85.1% in northern and 83.9% in central vs. 61.6% in southern China, P<0.001) and a similar trend was seen in all three age groups (P = 0.708, <0.001 and 0.025, respectively). In adolescents, the frequencies of isoniazid (INH)-resistant and ethambutol (EMB)-resistant isolates were significantly higher among Beijing strains compared to non-Beijing genotype strains (P = 0.028 for INH and P = 0.027 for EMB). Furthermore, strong association was observed between resistance to rifampicine (RIF), streptomycin (STR) and multidrug resistance (MDR) among Beijing compared to non-Beijing strains in previously treated cases of children (P = 0.01, 0.01 and 0.025, respectively).Conclusion/Significance
Beijing family was more prevalent in northern and central China compared to southern China and these strains were predominant in all age groups. The genetic diversity of M. tuberculosis isolates from children was similar to that found in adolescents and adults. Beijing genotype was associated with RIF, STR and MDR resistance in previously treated children. 相似文献98.
Ren‐Hua Chen Yi‐Gang Li Kun‐Li Jiao Peng‐Pai Zhang Yu Sun Li‐Ping Zhang Xiang‐Fei Fong Wei Li Yi Yu 《Journal of cellular and molecular medicine》2013,17(5):608-616
The expression of the chemorepellent Sema3a is inversely related to sympathetic innervation. We investigated whether overexpression of Sema3a in the myocardial infarction (MI) border zone could attenuate sympathetic hyper‐innervation and decrease the vulnerability to malignant ventricular tachyarrhythmia (VT) in rats. Survived MI rats were randomized to phosphate buffered saline (PBS, n = 12); mock lentivirus (MLV, n = 13) and lentivirus‐mediated overexpression of Sema3a (SLV, n = 13) groups. Sham‐operated rats served as control group (CON, n = 20). Cardiac function and electrophysiological study (PES) were performed at 1 week later. Blood and tissue samples were collected for histological analysis, epinephrine (EPI), growth‐associated factor 43 (GAP43) and tyrosine hydroxylase (TH) measurements. QTc intervals were significantly shorter in SLV group than in PBS and MLV groups (168.6 ± 7.8 vs. 178.1 ± 9.5 and 180.9 ± 8.2 ms, all P < 0.01). Inducibility of VT by PES was significantly lower in the SLV group [30.8% (4/13)] than in PBS [66.7% (8/12)] and MLV [61.5% (8/13)] groups (P < 0.05). mRNA and protein expressions of Sema3a were significantly higher and the protein expression of GAP43 and TH was significantly lower at 7 days after transduction in SLV group compared with PBS, MLV and CON groups. Myocardial EPI in the border zone was also significantly lower in SLV group than in PBS and MLV group (8.73 ± 1.30 vs. 11.94 ± 1.71 and 12.24 ± 1.54 μg/g protein, P < 0.001). Overexpression of Sema3a in MI border zone could reduce the inducibility of ventricular arrhythmias by reducing sympathetic hyper‐reinnervation after infarction. 相似文献
99.
Wei Gao Jiqing Jiao Huajie Feng Xiaopeng Xuan Liuping Chen 《Journal of molecular modeling》2013,19(3):1273-1283
A combined and sequential use of quantum mechanical (QM) calculations and classical molecular dynamics (MD) simulations was made to investigate the σ and π types of hydrogen bond (HB) in benzene-water and pyrrole-water as clusters and as their liquid mixture, respectively. This paper aims at analyzing similarities and differences of these HBs resulted from QM and MD on an equal footing. Based on the optimized geometry at ωb97xD/aug-cc-pVTZ level of theory, the nature and property of σ and π types of HBs are unveiled by means of atoms in molecules (AIM), natural bond orbital (NBO) and energy decomposition analysis (EDA). In light of the above findings, MD simulation with OPLS-AA and SPC model was applied to study the liquid mixture at different temperatures. The MD results further characterize the behavior and structural properties of σ and π types HBs, which are somewhat different but reasonable for the clusters by QM. Finally, we provide a reasonable explanation for the different solubility between benzene/water and pyrrole/water. Figure
The σ and π types of hydrogen bond as benzene-water and pyrrole-water clusters in gas; Snapshot of benzene/water and pyrrole/water as 1:1 liquid mixture extracted from the MD simulations 相似文献
100.
Jinrui Gan Kun Qian Jingjing Wan Liang Qiao Weichao Guo Pengyuan Yang Hubert H. Girault Baohong Liu 《Proteomics》2013,13(21):3117-3123
Amino‐functionalized macroporous silica foam (NH2‐MOSF) has been developed as a host reactor to realize highly efficient proteolysis in acidic solutions where normal tryptic reactions cannot occur. The digestion protocol consists simply of adding the functionalized NH2‐MOSF into the protein and trypsin solutions without altering the bulk pH or preloading the enzymes on the materials. With this protocol, digestion of sample fractions from LC can be efficiently realized in the acidic solutions directly. Digestion of a protein fraction extracted from rat liver tissue after LC separation was performed to illustrate this principle, where 103 proteins were successfully identified at pH 3 after 1.5 h of tryptic digestion. 相似文献