全文获取类型
收费全文 | 3204篇 |
免费 | 286篇 |
国内免费 | 101篇 |
专业分类
耳鼻咽喉 | 6篇 |
儿科学 | 5篇 |
妇产科学 | 20篇 |
基础医学 | 557篇 |
口腔科学 | 43篇 |
临床医学 | 111篇 |
内科学 | 384篇 |
皮肤病学 | 51篇 |
神经病学 | 356篇 |
特种医学 | 15篇 |
外国民族医学 | 1篇 |
外科学 | 143篇 |
综合类 | 290篇 |
预防医学 | 66篇 |
眼科学 | 31篇 |
药学 | 875篇 |
中国医学 | 202篇 |
肿瘤学 | 435篇 |
出版年
2024年 | 5篇 |
2023年 | 31篇 |
2022年 | 59篇 |
2021年 | 87篇 |
2020年 | 101篇 |
2019年 | 99篇 |
2018年 | 90篇 |
2017年 | 94篇 |
2016年 | 99篇 |
2015年 | 174篇 |
2014年 | 261篇 |
2013年 | 252篇 |
2012年 | 304篇 |
2011年 | 318篇 |
2010年 | 288篇 |
2009年 | 286篇 |
2008年 | 228篇 |
2007年 | 194篇 |
2006年 | 190篇 |
2005年 | 145篇 |
2004年 | 107篇 |
2003年 | 76篇 |
2002年 | 52篇 |
2001年 | 20篇 |
2000年 | 18篇 |
1999年 | 5篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1994年 | 1篇 |
1993年 | 1篇 |
排序方式: 共有3591条查询结果,搜索用时 46 毫秒
71.
《Connective tissue research》2013,54(6):497-509
We investigated whether the hyperbaric oxygen (O2) could promote the proliferation of growth-arrested osteoblasts in vitro and the mechanisms involved in this process. Osteoblasts were exposed to different combinations of saturation and pressure of O2 and evaluated at 3 and 7 days. Control cells were cultured under ambient O2 and normal pressure [1 atmosphere (ATA)]; high-pressure group cells were treated with high pressure (2.5 ATA) twice daily; high-O2 group cells were treated with a high concentration O2 (50% O2) twice daily; and high pressure plus high-O2 group cells were treated with high pressure (2.5 ATA) and a high concentration O2 (50% O2) twice daily. Hyperbaric O2 significantly promoted osteoblast proliferation and cell cycle progression after 3 days of treatment. Hyperbaric O2 treatment stimulated significantly increased mRNA expression of fibroblast growth factor (FGF)-2 as well as protein expression levels of Akt, p70S6K, phosphorylated ERK, nuclear factor (NF)-κB, protein kinase C (PKC)α, and phosphorylated c-Jun N-terminal kinase (JNK). Our findings indicate that high pressure and high O2 saturation stimulates growth-arrested osteoblasts to proliferate. These findings suggest that the proliferative effects of hyperbaric O2 on osteoblasts may contribute to the recruitment of osteoblasts at the fracture site. The FGF-2/MEK/ERK 1/2/Akt/p70S6K/NF-κB and PKC/JNK pathways may be involved in mediating this process. 相似文献
72.
《Expert opinion on investigational drugs》2013,22(8):1039-1045
Objective: The goal of this study is to investigate the effects of sorafenib on tumor growth, recurrence and metastasis after curative resection of liver cancer. Research methods: SMMC-7721 and HCCLM3 liver tumors, each with different metastatic potential and basal phosphorylated extracellular signal-regulated kinase (pERK) levels, were orthotopically implanted into 56 nude mice. Mice were divided into a treatment sub study and a prevention sub study. Results: In the treatment sub study, tumor volumes in the high pERK-expressing HCCLM3 model were 2.58 ± 0.83 and 0.38 ± 0.09 cm3 without and with sorafenib, respectively (p < 0.001). The corresponding volumes in the low pERK-expressing SMMC-7721 model were 1.36 ± 0.24 and 0.24 ± 0.14 cm3 (p < 0.001), respectively. Sorafenib inhibited HCCLM3 cell proliferation and decreased tumor angiogenesis, but did not inhibit proliferation in the SMMC-7721 model. In the prevention sub study, intrahepatic recurrent tumor volumes were 1.96 ± 0.45 and 0.18 ± 0.24 cm3 (p < 0.001); lung metastasis frequencies were 100 and 0% (p = 0.005); and lifespans were 36 ± 3 and 46 ± 5 days (p = 0.002) in the control and sorafenib subgroups, respectively. Conclusions: Sorafenib inhibits tumor growth and prevents metastatic recurrence after resection of hepatocellular carcinoma in nude mice. The effect of sorafenib does not exclusively depend on high levels of pERK in tumors. 相似文献
73.
Sotirios G. Zarogiannis Aristotelis S. Filippidis Solana Fernandez Asta Jurkuvenaite Namasivayam Ambalavanan Andrei Stanishevsky Yogesh K. Vohra Sadis Matalon 《Respiratory physiology & neurobiology》2013,185(2):454-460
Titanium dioxide engineered nanoparticles (nano-TiO2) are widely used in the manufacturing of a number of products. Due to their size (<100 nm), when inhaled they may be deposited in the distal lung regions and damage Clara cells. We investigated the mechanisms by which short-term (1-h) incubation of human airway Clara-like (H441) cells to nano-TiO2 (6 nm in diameter) alters the ability of H441 cells to adhere to extracellular matrix. Our results show that 1 h post-incubation, there was a 3-fold increase of extracellular H2O2, increased intracellular oxidative stress as demonstrated by 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) oxidation, and a 5-fold increase of phosphor-ERK1/2 as measured by Western blotting. These changes were accompanied by a 25% decrease of H441 adherence to fibronectin (p < 0.05 compared to vehicle incubated H441 cells). Pretreatment with the ERK1/2 inhibitor U0126 for 3 h, partially prevented this effect. In conclusion, short-term exposure of H441 cells to nano-TiO2 appears to reduce adherence to fibronectin due to oxidative stress and activation of ERK1/2. 相似文献
74.
《Journal of immunotoxicology》2013,10(4):298-307
The World Trade Center (WTC) collapse on September 11, 2001 released copious amounts of particulate matter (PM) into the atmosphere of New York City. Follow-up studies on persons exposed to the dusts have revealed a severely increased rate for asthma and other respiratory illnesses. There have only been a few studies that have sought to discern the possible mechanisms underlying these untoward pathologies. In one study, an increased cytokine release was detected in cells exposed to WTC fine dusts (PM2.5 fraction or WTC2.5). However, the mechanism(s) for these increases has yet to be fully defined. Because activation of the mitogen-activated protein kinase (MAPK) signaling pathways is known to cause cytokine induction, the current study was undertaken to analyze the possible involvement of these pathways in any increased cytokine formation by lung epithelial cells (as BEAS-2B cells) exposed to WTC2.5. Our results showed that exposure to WTC2.5 for 5?hr increased interleukin-6 (IL-6) mRNA expression in BEAS-2B cells, as well as its protein levels in the culture media, in a dose-dependent manner. Besides IL-6, cytokine multiplex analyses revealed that formation of IL-8 and -10 was also elevated by the exposure. Both extracellular signal-regulated kinase (ERK) and p38, but not c-Jun N-terminal protein kinase, signaling pathways were found to be activated in cells exposed to WTC2.5. Inactivation of ERK signaling pathways by PD98059 effectively blocked IL-6, -8, and -10 induction by WTC2.5; the p38 kinase inhibitor SB203580 significantly decreased induction of IL-8 and -10. Together, our data demonstrated activation of MAPK signaling pathway(s) likely played an important role in the WTC2.5-induced formation of several inflammatory (and, subsequently, anti-inflammatory) cytokines. The results are important in that they help to define one mechanism via which the WTC dusts may have acted to cause the documented increases in asthma and other inflammation-associated respiratory dysfunctions in the individuals exposed to the dusts released from the WTC collapse. 相似文献
75.
76.
《Renal failure》2013,35(7):971-977
AbstractThis study explored the effects of caveolin-1, p-ERK1/2 and transient receptor potential channel 6 (TRPC6) on angiotensin II (Ang II)-induced glomerular mesangial cell (GMC) proliferation, and investigated the role of Ang II on GMC proliferation. GMC cultures were divided into Control, Ang II (Ang II 10?7?mol/L), PD98059 (Ang II 10?7?mol/L?+?PD98059 5?×?10?5?mol/L) and MβCD groups (Ang II 10?7?mol/L?+?MβCD 10?2?mol/L). GMCs proliferation was measured by the methyl thiazolil tetracolium and trypan blue assays. The distribution of caveolin-1, p-ERK1/2 and TRPC6 was monitored by immunocytochemistry. Real time polymerase chain reaction (PCR) was used to assess mRNA expression of caveolin-1 and TRPC6. Western blot analysis was used to assess protein expression of caveolin-1, p-ERK1/2 and TRPC6. The results showed that Ang II promoted GMC proliferation. PD98059 and MβCD blocked Ang II-induced GMC proliferation, by 31.06% and 48.96%, respectively. In comparison with the control group, the expression of p-ERK1/2 and TRPC6 was significantly higher and caveolin-1 expression was significantly lower in the Ang II group. PD98059 markedly decreased p-ERK1/2 and TRPC6 expression and increased caveolin-1 expression. MβCD decreased the expression of p-ERK1/2 and TRPC6, but had no significant effect on caveolin-1 protein expression. These findings suggested that the intact caveolae structure was associated with Ang II-induced GMC proliferation, ERK1/2 activation and TRPC6 expression. And p-ERK1/2 acted as an upstream signal molecule for TRPC6. Moreover, p-ERK1/2 and caveolin-1 appeared to be inhibited reciprocally, thus regulated GMC proliferation by regulating TRPC6 expression. 相似文献
77.
Tammy A. Butterick Joshua P. Nixon Charles J. Billington Catherine M. Kotz 《Neuroscience letters》2012
Current data support the idea that hypothalamic neuropeptide orexin A (OxA; hypocretin 1) mediates resistance to high fat diet-induced obesity. We previously demonstrated that OxA elevates spontaneous physical activity (SPA), that rodents with high SPA have higher endogenous orexin sensitivity, and that OxA-induced SPA contributes to obesity resistance in rodents. Recent reports show that OxA can confer neuroprotection against ischemic damage, and may decrease lipid peroxidation. This is noteworthy as independent lines of evidence indicate that diets high in saturated fats can decrease SPA, increase hypothalamic apoptosis, and lead to obesity. Together data suggest OxA may protect against obesity both by inducing SPA and by modulation of anti-apoptotic mechanisms. While OxA effects on SPA are well characterized, little is known about the short- and long-term effects of hypothalamic OxA signaling on intracellular neuronal metabolic status, or the physiological relevance of such signaling to SPA. To address this issue, we evaluated the neuroprotective effects of OxA in a novel immortalized primary embryonic rat hypothalamic cell line. We demonstrate for the first time that OxA increases cell viability during hydrogen peroxide challenge, decreases hydrogen peroxide-induced lipid peroxidative stress, and decreases caspase 3/7 induced apoptosis in an in vitro hypothalamic model. Our data support the hypothesis that OxA may promote obesity resistance both by increasing SPA, and by influencing survival of OxA-responsive hypothalamic neurons. Further identification of the individual mediators of the anti-apoptotic and peroxidative effects of OxA on target neurons could lead to therapies designed to maintain elevated SPA and increase obesity resistance. 相似文献
78.
Mario Salmeri Carla Motta Silvana Mastrojeni Andrea Amodeo Carmelina Daniela Anfuso Giovanni Giurdanella Angela Morello Mario Alberghina Maria Antonietta Toscano Gabriella Lupo 《Neuroscience letters》2012
Escherichia coli K1 is the most common Gram-negative organism that causes neonatal meningitis following penetration of the blood–brain barrier. In the present study we demonstrated the involvement of cytosolic (cPLA2) and calcium-independent phospholipase A2 (iPLA2) and the contribution of cyclooxygenase-2 products in E. coli invasion of microvascular endothelial cells. The traversal of bacteria did not determine trans-endothelial electrical resistance (TEER) and ZO-1 expression changes and was reduced by PLA2s siRNA. cPLA2 and iPLA2 enzyme activities and cPLA2 phosphorylation were stimulated after E. coli incubation and were attenuated by PLA2, PI3-K, ERK 1/2 inhibitors. Our results demonstrate the role of PKCα/ERK/MAPK signaling pathways in governing the E. coli penetration into the brain. 相似文献
79.
A natural antioxidant,tannic acid mitigates iron‐overload induced hepatotoxicity in Swiss albino mice through ROS regulation 下载免费PDF全文
《Environmental toxicology》2018,33(5):603-618
Tannic acid (TA), a water soluble natural polyphenol with 8 gallic acids groups, is abundantly present in various medicinal plants. Previously TA has been investigated for its antimicrobial and antifungal properties. Being a large polyphenol, TA chelates more than 1 metal. Hence TA has been explored for potent antioxidant activities against reactive oxygen species (ROS), reactive nitrogen species (RNS) and as iron chelator in vitro thereby mitigating iron‐overload induced hepatotoxicity in vivo. Iron dextran was injected intraperitoneally in Swiss albino mice to induce iron‐overload triggered hepatotoxicity, followed by oral administration of TA for remediation. After treatment, liver, spleen, and blood samples were processed from sacrificed animals. The liver iron, serum ferritin, serum markers, ROS, liver antioxidant status, and liver damage parameters were assessed, followed by histopathology and protein expression studies. Our results show that TA is a prominent ROS and RNS scavenger as well as iron chelator in vitro. It also reversed the ROS levels in vivo and restricted the liver damage parameters as compared to the standard drug, desirox. Moreover, this natural polyphenol exclusively ameliorates the histopathological and fibrotic changes in liver sections reducing the iron‐overload, along with chelation of liver iron and normalization of serum ferritin. The protective role of TA against iron‐overload induced apoptosis in liver was further supported by changed levels of caspase 3, PARP as well as Bax/BCl‐2 ratio. Thus, TA can be envisaged as a better orally administrable iron chelator to reduce iron‐overload induced hepatotoxicity through ROS regulation. 相似文献
80.