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991.
992.
Zhang Yong Xia Qin Jian Sun Hua Yang Ming Xia Zhang Ru Ban Ge Lin Xu Ya Ping Wu Le Xin Wang Yi Feng Du 《PloS one》2015,10(6)
Background and Objectives
Carotid artery stenting (CAS) is an important therapeutic strategy for patients with carotid artery stenosis. However, the potential influence of CAS on cognitive function in patients with carotid artery stenosis and cerebral lacunar infarction has not been determined. This study investigated changes in cognitive function associated with CAS and the factors related to these changes.Methods
This prospective cohort study comprised 579 Chinese patients with cerebral lacunar infarction and carotid artery stenosis for whom CAS was indicated, and a matched control group of 552 healthy individuals. Cognitive function before CAS and at scheduled intervals from 6 months to 3 years was assessed with instruments that included the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scale. Potential factors that might affect cognitive function were analyzed via logistic regression.Results
The MMSE and MoCA scores of the patients before CAS were significantly lower than that of the control subjects. These scores were significantly higher 6 months after CAS and sustained or increased throughout the 3-year follow-up. Also significantly improved after CAS from baseline were scores for an alternating trail test, cube copying, clock-drawing, attention, and delayed recall in an auditory-verbal learning test. Logistic regression analyses showed that age greater than 65 y, little education, diabetes, and hypertension were independent risk factors for deteriorated MoCA scores 3 years after CAS.Conclusion
CAS was associated with significantly improved cognitive function in cerebral lacunar infarction patients with severe stenosis. 相似文献993.
Shugang Li Mengchuan Xu Qiang Niu Shangzhi Xu Yusong Ding Yizhong Yan Shuxia Guo Feng Li 《PloS one》2015,10(10)
Aims
In this study, the efficacy of proanthocyanidins (PCs) against oxidative damage was systematically reviewed to facilitate their use in various applications.Methods
A meta-analysis was performed by two researchers. Each investigator independently searched electronic databases, including Cochrane, PubMed, Springer, Web of Science, China National Knowledge Infrastructure (CKNI), China Science and Technology Journal Database (CSTJ), and WanFang Data, and analyzed published data from 29 studies on the effects of PCs against oxidative damage. Oxidative stress indexes included superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), and total antioxidative capacity (T-AOC).Results
Compared with the oxidative damage model group, PCs effectively improved the T-AOC, SOD, GSH, GPx, and CAT levels, and reduced the MDA levels; these differences were statistically significant (P < 0.05). In studies that used the gavage method, SOD (95% CI, 2.33–4.00) and GPx (95% CI, 2.10–4.05) were 3.16-fold and 3.08-fold higher in the PC group than in the control group, respectively. In studies that used the feeding method, SOD (95% CI, 0.32–1.74) and GPx (95% CI, -0.31 to 1.65) were 1.03-fold and 0.67-fold higher in the PC group than in the control group, respectively. Statistically significant differences in the effects of PCs (P < 0.00001) were observed between these two methods. MDA estimated from tissue samples (95% CI, -5.82 to -2.60) was 4.32-fold lower in the PC group than in the control group. In contrast, MDA estimated using serum samples (95% CI, -4.07 to -2.06) was 3.06-fold lower in the PC group than in the control group. The effect of PCs on MDA was significantly greater in tissue samples than in serum samples (P = 0.02).Conclusion
PCs effectively antagonize oxidative damage and enhance antioxidant capacity. The antagonistic effect may be related to intervention time, intervention method, and the source from which the indexes are estimated. 相似文献994.
Kun Song Wei Hu Fei Yue Jing Zou Wenjiao Li Qi Chen Qizhi Yao Weijia Sun Leyuan Liu 《PloS one》2015,10(11)
Background and Aim
Autophagy is a cellular process to regulate the turnover of misfolded/aggregated proteins or dysfunctional organelles such as damaged mitochondria. Microtubule-associated protein MAP1S (originally named C19ORF5) is a widely-distributed homologue of neuronal-specific MAP1A and MAP1B with which autophagy marker light chain 3 (LC3) was originally co-purified. MAP1S bridges autophagic components with microtubules and mitochondria through LC3 and positively regulates autophagy flux from autophagosomal biogenesis to degradation. The MAP1S-mediated autophagy suppresses tumorigenesis as suggested in a mouse liver cancer model and in prostate cancer patients. The TGFβ signaling pathway plays a central role in pancreatic tumorigenesis, and high levels of TGFβ suggest a tumor suppressive function and predict a better survival for some patients with resectable pancreatic ductal adenocarcinoma. In this study, we try to understand the relationship between TGFβ and MAP1S-mediated autophagy in pancreatic ductal adenocarcinoma.Methods
We collected the tumor and its adjacent normal tissues from 33 randomly selected patients of pancreatic ductal adenocarcinomas to test the association between TGFβ and autophagy markers MAP1S and LC3. Then we tested the cause and effect relation between TGFβ and autophagy markers in cultured pancreatic cancer cell lines.Results
Here we show that levels of TGFβ and autophagy markers MAP1S and LC3 are dramatically elevated in tumor tissues from patients with pancreatic ductal adenocarcinomas. TGFβ increases levels of MAP1S protein and enhances autophagy flux.Conclusion
TGFβ may suppress the development of pancreatic ductal adenocarcinomas by enhancing MAP1S-mediated autophagy. 相似文献995.
Feng Gao Xiangyu Xiong Wenting Pan Xinyu Yang Changchun Zhou Qipeng Yuan Liqing Zhou Ming Yang 《PloS one》2015,10(8)
A functional rs4245739 A>C single nucleotide polymorphism (SNP) locating in the MDM43’-untranslated (3’-UTR) region creates a miR-191-5p or miR-887-3p targeting sites. This change results in decreased expression of oncogene MDM4. Therefore, we examined the association between this SNP and small cell lung cancer (SCLC) risk as well as its regulatory function in SCLC cells. Genotypes were determined in two independent case-control sets consisted of 520SCLC cases and 1040 controls from two regions of China. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. The impact of the rs4245739 SNP on miR-191-5p/miR-887-3p mediated MDM4 expression regulation was investigated using luciferase reporter gene assays. We found that the MDM4 rs4245739AC and CC genotypes were significantly associated with decreased SCLC susceptibility compared with the AA genotype in both case-control sets (Shandong set: OR = 0.53, 95% CI = 0.32–0.89, P = 0.014; Jiangsu set: OR = 0.47, 95% CI = 0.26–0.879, P = 0.017). Stratified analyses indicated that there was a significantly multiplicative interaction between rs4245739 and smoking (P
interactioin = 0.048). After co-tranfection of miRNAs and different allelic-MDM4 reporter constructs into SCLC cells, we found that the both miR-191-5p and miR-887-3p can lead to significantly decreased MDM4 expression activities in the construct with C-allelic 3’-UTR but not A-allelic 3’-UTR, suggesting a consistent genotype-phenotype correlation. Our data illuminate that the MDM4rs4245739SNP contributes to SCLC risk and support the notion that gene 3’-UTR genetic variants, impacting miRNA-binding, might modify SCLC susceptibility. 相似文献
996.
Sirtuin 1 (Sirt1) is an NAD+-dependent protein deacetylase that is proposed to mediate many health-promoting effects of calorie restriction (CR). We recently reported that short-term CR increased the bile acid (BA) pool size in mice, likely due to increased BA synthesis in liver. Given the important role of Sirt1 in the regulation of glucose, lipid, as well as BA metabolism, we hypothesized that the CR-induced increase in BAs is Sirt1-dependent. To address this, the present study utilized genetically-modified mice that were Sirt1 loss of function (liver knockout, LKO) or Sirt1 gain of function (whole body-transgenic, TG). Three genotypes of mice (Sirt1-LKO, wild-type, and Sirt1-TG) were each randomly divided into ad libitum or 40% CR feeding for one month. BAs were extracted from various compartments of the enterohepatic circulation, followed by BA profiling by UPLC-MS/MS. CR increased the BA pool size and total BAs in serum, gallbladder, and small intestine. The CR-induced increase in BA pool size correlated with the tendency of increase in the expression of the rate-limiting BA-synthetic enzyme Cyp7a1. However, in contrast to the hypothesis, the CR-induced increase in BA pool size and Cyp7a1 expression was still observed with ablated expression of Sirt1 in liver, and completely suppressed with whole-body overexpression of Sirt1. Furthermore, in terms of BA composition, CR increased the ratio of 12α-hydroxylated BAs regardless of Sirt1 genotypes. In conclusion, the CR-induced alterations in BA pool size, BA profiles, and expression of BA-related genes do not appear to be dependent on Sirt1. 相似文献
997.
Jen-Yin Chen Li-Kai Wang Ping-Hsun Feng Chin-Chen Chu Tain-Junn Cheng Shih-Feng Weng Su-Zhen Wu Tsung-Hsueh Lu Chia-Yu Chang 《PloS one》2015,10(8)
Background
Primary Sjögren''s syndrome (pSS) is associated with immunological dysfunctions—a well-known risk factor of shingles. This study aimed to examine the incidence and risk of shingles in adults with pSS and pharmacological treatments.Methods
This retrospective population-based cohort study was conducted using National Health Insurance claims data. Using propensity scores, 4,287 pSS adult patients and 25,722-matched cohorts by age, gender, selected comorbidities and Charlson comorbidity index scores were identified. Kaplan-Meier analysis and Cox regression were conducted to compare the differences in developing shingles. In pSS, oral and eye dryness are treated with substitute agents. Extraglandular features are often treated with pharmacological drugs including steroids and immunosuppressants. pSS patients were grouped as follows: no pharmacological drugs, steroids alone; immunosuppressants alone; combined therapies.Results
During the follow-up, 463 adults with pSS (10.80%) and 1,345 control cohorts (5.23%) developed shingles. The cumulative incidence of shingles in pSS patients (18.74/1,000 patient-years) was significantly higher than controls (8.55/1,000 patient-years). The adjusted hazard ratio (HR) of shingles was 1.69 (95% confidence interval (CI) 1.50–1.90). In age-subgroup analyses, incidences of shingles in pSS increased with age and peaked in pSS patients aged ≧60; however, adjusted HRs decreased with age. Compared to control cohorts with no drugs, adjusted HRs for shingles in pSS patients were ranked from high to low as: combined therapies (4.14; 95% CI 3.14–5.45) > immunosuppressants alone (3.24; 95% CI 2.36–4.45) > steroids alone (2.54; 95% CI 2.16–2.97) > no pharmacological drugs (2.06; 95% CI 1.76–2.41). Rates of shingles-associated hospitalization and postherpetic neuralgia were 5.62% and 24.41%, both of which were significantly higher than those (2.60%; 13.01%) in the control cohorts.Conclusions
Adults with pSS were at greater risk for shingles than control cohorts. Drug exposures significantly increased the risk of shingles in pSS. 相似文献998.
999.
The development of novel targeted therapies holds promise for conquering chemotherapy resistance, which is one of the major hurdles in current breast cancer treatment. Previous studies indicate that mitochondria uncoupling protein 2 (UCP-2) is involved in the development of chemotherapy resistance in colon cancer and lung cancer cells. In the present study we found that lower level of miR133a is accompanied by increased expression of UCP-2 in Doxorubicin-resistant breast cancer cell cline MCF-7/Dox as compared with its parental cell line MCF-7. We postulated that miR133a might play a functional role in the development of Doxorubicin-resistant in breast cancer cells. In this study we showed that: 1) exogenous expression of miR133a in MCF-7/Dox cells can sensitize their reaction to the treatment of Doxorubicin, which is coincided with reduced expression of UCP-2; 2) knockdown of UCP-2 in MCF-7/Dox cells can also sensitize their reaction to the treatment of Doxorubicin; 3) intratumoral delivering of miR133a can restore Doxorubicin treatment response in Doxorubicin-resistant xenografts in vivo, which is concomitant with the decreased expression of UCP-2. These findings provided direct evidences that the miR133a/UCP-2 axis might play an essential role in the development of Doxorubicin-resistance in breast cancer cells, suggesting that the miR133a/UCP-2 signaling cohort could be served as a novel therapeutic target for the treatment of chemotherapy resistant in breast cancer. 相似文献
1000.
Xiaoyu Jiang Liya Yuan John A. Engelbach Jeremy Cates Carlos J. Perez-Torres Feng Gao Dinesh Thotala Robert E. Drzymala Robert E. Schmidt Keith M. Rich Dennis E. Hallahan Joseph J. H. Ackerman Joel R. Garbow 《PloS one》2015,10(10)