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   1466篇
  免费   148篇
  国内免费   167篇
  2024年   2篇
  2023年   27篇
  2022年   49篇
  2021年   77篇
  2020年   62篇
  2019年   78篇
  2018年   77篇
  2017年   67篇
  2016年   92篇
  2015年   116篇
  2014年   119篇
  2013年   127篇
  2012年   132篇
  2011年   119篇
  2010年   79篇
  2009年   66篇
  2008年   77篇
  2007年   60篇
  2006年   63篇
  2005年   33篇
  2004年   38篇
  2003年   30篇
  2002年   32篇
  2001年   19篇
  2000年   16篇
  1999年   27篇
  1998年   6篇
  1997年   4篇
  1995年   4篇
  1994年   8篇
  1993年   7篇
  1992年   13篇
  1991年   8篇
  1990年   3篇
  1989年   4篇
  1988年   6篇
  1987年   7篇
  1985年   4篇
  1984年   3篇
  1983年   2篇
  1981年   2篇
  1980年   1篇
  1979年   1篇
  1978年   1篇
  1975年   2篇
  1974年   3篇
  1973年   2篇
  1971年   1篇
  1969年   1篇
  1968年   2篇
排序方式: 共有1781条查询结果,搜索用时 15 毫秒
41.
This study delineates the role of peroxiredoxin 3 (Prx3) in hair cell death induced by several etiologies of acquired hearing loss (noise trauma, aminoglycoside treatment, age). In vivo, Prx3 transiently increased in mouse cochlear hair cells after traumatic noise exposure, kanamycin treatment, or with progressing age before any cell loss occurred; when Prx3 declined, hair cell loss began. Maintenance of high Prx3 levels via treatment with the radical scavenger 2,3-dihydroxybenzoate prevented kanamycin-induced hair cell death. Conversely, reducing Prx3 levels with Prx3 siRNA increased the severity of noise-induced trauma. In mouse organ of Corti explants, reactive oxygen species and levels of Prx3 mRNA and protein increased concomitantly at early times of drug challenge. When Prx3 levels declined after prolonged treatment, hair cells began to die. The radical scavenger p-phenylenediamine maintained Prx3 levels and attenuated gentamicin-induced hair cell death. Our results suggest that Prx3 is up-regulated in response to oxidative stress and that maintenance of Prx3 levels in hair cells is a critical factor in their susceptibility to acquired hearing loss.  相似文献   
42.

Background and Objective

Emerging evidence indicates that common functional polymorphisms in the estrogen receptor 1 (ESR1) gene may have an impact on an individual’s susceptibility to endometrial cancer, but individually published results are inconclusive. The aim of this meta-analysis is to derive a more precise estimation of the associations between eight polymorphisms in the ESR1 gene and endometrial cancer risk.

Methods

A literature search of PubMed, Embase, Web of Science and China Biology Medicine (CBM) databases was conducted on publications published before November 1st, 2012. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Statistical analyses were performed using the STATA 12.0 software.

Results

Thirteen case-control studies were included with a total of 7,649 endometrial cancer cases and 16,855 healthy controls. When all the eligible studies were pooled into the meta-analysis, the results indicated that PvuII (C>T) polymorphism was associated with an increased risk of endometrial cancer, especially among Caucasian populations. There were also significant associations between rs3020314 (C>T) polymorphism and an increased risk of endometrial cancer. Furthermore, rs2234670 (S/L) polymorphism may decrease the risk of endometrial cancer. However, no statistically significant associations were found in XbaI (A>G), Codon 325 (C>G), Codon 243 (C>T), VNTR (S/L) and rs2046210 (G>A) polymorphisms.

Conclusion

The current meta-analysis suggests that PvuII (C>T) and rs3020314 (C>T) polymorphisms may be risk factors for endometrial cancer, especially among Caucasian populations.  相似文献   
43.
44.
Histone deacetylase 4 (HDAC4) is a member of the HDACs family, its expression is closely related to the cell development. The cell is an independent living entity that undergoes proliferation, differentiation, senescence, apoptosis, and pathology, and each process has a strict and complex regulatory system. With deepening of its research, the expression of HDAC4 is critical in the life process. This review focuses on the posttranslational modification of HDAC4 in cell biology, providing an important target for future disease treatment.  相似文献   
45.
Wang  Hongjun  Li  Mingze  Cui  Haibin  Song  Xiangyuan  Sha  Qian 《Neurochemical research》2020,45(11):2691-2702
Neurochemical Research - Retinoblastoma (RB) is a common intraocular malignant tumor. The growing evidence has reported that circular RNAs (circRNAs) play critical roles in RB development....  相似文献   
46.
Chromoblastomycosis is one of the most frequent chronic infections caused by melanized fungi. In order to evaluate the clinical characteristics of chromoblastomycosis in Mainland China, we performed an evidence-based review of published literature. PubMed and Chinese-language database of CNKI, VIP and Wanfang data during January 1990–August 2011 were searched. Epidemiology, clinical features, laboratory findings, therapy and prognosis were analyzed. Cladophialophora carrionii was the most common causative agent in the north of the Mainland China, and Fonsecaea monophora and F. pedrosoi were the most common agents in the southern part of the Mainland China. Infection commonly initiated after the etiologic agents gain entrance through puncture wounds and more common involved extremities of the males. Skin lesions were found in different sites, like the extremities, buttocks, trunk and face, and presented diversity morphology. There were about seven different clinical types found in Mainland China: plaque type, tumoral type, cicatricial type, verrucous type, pseudo-vacuole type, eczymatous type and mixed type of lesions. The success of treatment for chromoblastomycosis was related to the causative agent, the clinical form and severity of the lesions. Most of the patients could be treated successfully with the physical treatment, chemotherapy and/or combination therapy. The itraconazole, terbinafine or a combination of both were commonly medication for these mycosis patients. Physical methods were usually indicated to support chemotherapy with some severe forms and long-lasting cases. Photodynamic therapy has been extended from the oncological field to that of antimicrobial chemotherapy in these years. We applied it on some recalcitrant cases of chromoblastomycosis and found its good clinical response, and hopeful it could be a promising therapy in near future.  相似文献   
47.
Surplus male proboscis monkeys at the Singapore Zoo pose a considerable problem for maintenance and maximizing of exhibition potential. In 2008, a new exhibit was constructed to house and display a group of six proboscis monkey males born in Singapore Zoo. To document and monitor the all‐male group establishment in the new exhibit, we conducted observations on intragroup interactions between the monkeys, spatial use of their new exhibit, and visitor effects on their behavior. We found contact aggressive interactions between the monkeys to be consistently lower than noncontact aggressive interactions and by week six of introduction to the new exhibit, contact aggression was almost nonevident. Affiliative interactions also developed between individuals in the group, with an interface of aggressive and socioreconcilatory behavior influenced by food competition and a dominance hierarchy. This was evident from significantly higher overall aggression and affiliation during feeding times compared to nonfeeding times, and this was reduced when food competition was mitigated by modifying the feeding regime. We measured the groups’ spatial use of the exhibit and the relation to behavior, crowd size, and density. Our results showed that the proboscis monkeys utilized the available exhibit space, were largely unaffected by visitor crowd size and density, and were able to exhibit a variety of natural behaviors, including swimming. Our accomplishment in maintaining and displaying an all‐male group of proboscis monkeys in captivity provides viable options for more comprehensive captive management and breeding programs for this endangered species. Zoo Biol. 32:281‐290, 2013. © 2012 Wiley Periodicals, Inc.  相似文献   
48.
Quantifying Salmonella Population Dynamics in Water and Biofilms   总被引:1,自引:0,他引:1  
Members of the bacterial genus Salmonella are recognized worldwide as major zoonotic pathogens often found to persist in non-enteric environments including heterogeneous aquatic biofilms. In this study, Salmonella isolates that had been detected repeatedly over time in aquatic biofilms at different sites in Spring Lake, San Marcos, Texas, were identified as serovars Give, Thompson, Newport and -:z10:z39. Pathogenicity results from feeding studies with the nematode Caenorhabditis elegans as host confirmed that these strains were pathogenic, with Salmonella-fed C. elegans dying faster (mean survival time between 3 and 4 days) than controls, i.e., Escherichia coli-fed C. elegans (mean survival time of 9.5 days). Cells of these isolates inoculated into water at a density of up to 106?ml?1 water declined numerically by 3 orders of magnitude within 2 days, reaching the detection limit of our quantitative polymerase chain reaction (qPCR)-based quantification technique (i.e., 103 cells ml?1). Similar patterns were obtained for cells in heterogeneous aquatic biofilms developed on tiles and originally free of Salmonella that were kept in the inoculated water. Cell numbers increased during the first days to more than 107 cells cm?2, and then declined over time. Ten-fold higher cell numbers of Salmonella inoculated into water or into biofilm resulted in similar patterns of population dynamics, though cells in biofilms remained detectable with numbers around 104 cells cm?2 after 4 weeks. Independent of detectability by qPCR, samples of all treatments harbored viable salmonellae that resembled the inoculated isolates after 4 weeks of incubation. These results demonstrate that pathogenic salmonellae were isolated from heterogeneous aquatic biofilms and that they could persist and stay viable in such biofilms in high numbers for some time.  相似文献   
49.
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized pathologically by the abnormal deposition of extracellular amyloid-β (Aβ) oligomers. However, the nature and precise mechanism of the toxicity of Aβ oligomers are not clearly understood. Aβ oligomers have been previously shown to cause a major loss of EphB2, a member of the EphB family of receptor tyrosine kinases. To determine the effect of EphB2 on Aβ oligomer-induced neurotoxicity and the underlying molecular mechanisms, we examined the EphB2 gene in cultured hippocampal neurons. Using a cellular model of AD, Aβ1–42 oligomers were confirmed to induce neurotoxicity in a time-dependent manner and result in a major decrease of EphB2. EphB2 overexpression could prevent the neurotoxicity of hippocampal neurons from exposure to Aβ1–42 oligomers for 1 h. Further analysis revealed that EphB2 overexpression increased synaptic NR1 and NR2B expression in Aβ1–42 oligomer-treated neurons. Moreover, EphB2 overexpression prevented Aβ1–42 oligomer-induced downregulation of dephosphorylated p38 MAPK and phosphorylated CREB. Together, these results suggest that EphB2 is a factor which protects hippocampal neurons against the toxicity of Aβ1–42 oligomers, and we infer that the protection of EphB2 is achieved by increasing the synaptic NMDA receptor level and downstream p38 MAPK and CREB signaling in hippocampal neurons. This study provides new molecular insights into the neuroprotective effect of EphB2 and highlights its potential therapeutic role in the management of AD.  相似文献   
50.
The alleviative effects of exogenous calcium on copper phytotoxicity were investigated in Elodea canadensis plants. There was a significant accumulation of Cu in the plants after their exposure to 0.01 mM Cu accompanied by many symptoms of toxicity. Increased uptake of Cu severely reduced content of photosynthetic pigments, soluble proteins, and free proline. The total antioxidant capacity (T-AOC), reduced glutathione (GSH), and non-protein thiol (NP-SH) were severely suppressed in Cu-stressed plants resulting in a rapid increase in content of superoxide anion (O2 ·?), hydrogen peroxide, lipid peroxidation, and cell death. Simultaneous application of Ca markedly increased the content of photosynthetic pigments, soluble proteins, free proline, T-AOC, GSH, and NP-SH, and reduced oxidative damage as indicated by lowered content of MDA, O2 ·?, and H2O2; and decreased cell death. Furthermore, application of Ca reduced Cu uptake and effectively reversed the Cu-induced nutrient imbalance.  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