全文获取类型
收费全文 | 1229篇 |
免费 | 100篇 |
国内免费 | 14篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 10篇 |
妇产科学 | 13篇 |
基础医学 | 129篇 |
口腔科学 | 22篇 |
临床医学 | 64篇 |
内科学 | 168篇 |
皮肤病学 | 6篇 |
神经病学 | 79篇 |
特种医学 | 11篇 |
外国民族医学 | 1篇 |
外科学 | 70篇 |
综合类 | 84篇 |
预防医学 | 36篇 |
眼科学 | 4篇 |
药学 | 335篇 |
中国医学 | 129篇 |
肿瘤学 | 179篇 |
出版年
2023年 | 5篇 |
2022年 | 7篇 |
2021年 | 13篇 |
2020年 | 13篇 |
2019年 | 27篇 |
2018年 | 28篇 |
2017年 | 36篇 |
2016年 | 42篇 |
2015年 | 32篇 |
2014年 | 90篇 |
2013年 | 103篇 |
2012年 | 78篇 |
2011年 | 116篇 |
2010年 | 80篇 |
2009年 | 96篇 |
2008年 | 93篇 |
2007年 | 100篇 |
2006年 | 69篇 |
2005年 | 70篇 |
2004年 | 76篇 |
2003年 | 58篇 |
2002年 | 51篇 |
2001年 | 26篇 |
2000年 | 6篇 |
1999年 | 3篇 |
1998年 | 9篇 |
1997年 | 5篇 |
1996年 | 3篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 1篇 |
1991年 | 1篇 |
1982年 | 1篇 |
排序方式: 共有1343条查询结果,搜索用时 46 毫秒
91.
92.
The objectives of this focused review are to (i) provide a systematic overview of recent advances pertaining to the role of glia, namely microglia and astrocytes, in the neuropathology associated with excessive exposure to manganese (Mn), (ii) highlight possible mechanisms and factors involved in Mn-modulated, glia-derived neuroinflammation, and (iii) discuss the implications of excessive neuroinflammation on neuronal injury within the context of Mn overexposure. As this is not meant to be a comprehensive review on the topic of Mn neurotoxicity, the reader may wish to refer to several broader and more comprehensive reviews. After a brief introduction to Mn neurotoxicity, we first discuss the role of glial cells in neurodegeneration. Next, we review existing in vitro and in vivo studies that implicate Mn as a modulator of glial activation and ensuing neuroinflammation. This is followed by an examination of recognized and potential mechanisms that are involved in the modulation of glial inflammatory output by Mn; here the common pathways activated by Mn in glial and neuronal cells, including outcomes of such activation, are also addressed. We finish with a discussion of the implications of Mn-modulated glial activation for neuronal survival and with a list of data gaps in the topic that need to be filled in the future. 相似文献
93.
BackgroundNon-steroidal anti-inflammatory drugs (NSAIDs) act by inhibition of cyclooxygenase-2 (COX-2), which is overexpressed in cancer. The role of COX-2 and apoptosis were evaluated in 9,10-dimethylbenz(a)anthracene (DMBA)-induced lung cancer in rat and chemoprevention with indomethacin, a traditional NSAID and etoricoxib, a selective COX-2 inhibitor.MethodsThe animals were divided into Control, DMBA, DMBA + indomethacin and DMBA + etoricoxib groups. They received a single intratracheal instillation of DMBA while NSAIDs were given orally daily for 32 weeks. Besides morphology and histology of lungs, RT-PCR, western blots and immunohistochemistry were performed for the expression of apoptotic proteins and COX enzymes. Apoptosis was studied by DNA fragmentation and fluorescent staining.ResultsThe occurrence of tumors and lesions was noted in the DMBA animals, besides constricted alveolar spaces and hyperplasia. COX-1 was found to be uniformly expressed while COX-2 level was raised significantly in DMBA group. The apoptotic proteins, apaf-1, caspase-9 and caspase-3 were highly diminished in DMBA group but restored to normal level in NSAIDs groups. Also, apoptosis was suppressed in carcinogen group by DNA fragmentation analysis and fluorescent staining of the lung cells while coadministration of NSAIDs along with DMBA led to the restoration of apoptosis.ConclusionDMBA administration to the rats led to tumorigenesis in the lungs, had no effects on COX-1 expression, while elevating the COX-2 levels and suppressing apoptosis. The treatment with NSAIDs led to the amelioration of these effects. However, etoricoxib which is a COX-2 specific inhibitor, was found to be more effective than the traditional NSAID, indomethacin. 相似文献
94.
Akritopoulos P Papaioannidou P Hatzokos I Haritanti A Iosifidou E Kotoula M Mirtsou-Fidani V 《Archives of orthopaedic and trauma surgery》2009,129(10):1427-1432
Introduction Selective and non-selective cyclo-oxygenase (COX) inhibitors impair bone healing by inhibiting prostaglandin synthesis. The
purpose of this study was to evaluate the long-term effect of parecoxib, a selective COX-2 inhibitor, on bone healing in rats,
when it is applied in a pattern similar to clinical treatment patterns, that is, in a high dose and for a short period after
bone fracture.
Method Closed non-displaced mid-diaphyseal fractures in the middle of the left femoral shaft were generated in each animal. In the
study group, parecoxib sodium (1.06 mg/kg) was administered intra-peritoneally every day for 7 days. In the control group,
normal saline was administered intra-peritoneally every day for 7 days. In both groups fracture healing (bone union and callus
formation) was evaluated with X-rays 28 and 42 days after surgery.
Results Bone healing was lower in the study group (60 vs. 80% in the control group 28 days after fracture and 80 vs. 90% 42 days after
fracture) but this difference was not statistically significant (P > 0.05).
Conclusion Parecoxib does not have a significant long-term effect on bone healing in rats, when it is administered in a high dose and
for a short period after bone fracture.
Declaration The experiments comply with the current laws of the EU, and the protocol was approved by the Local Ethics Committee on Animal
Research. 相似文献
95.
Eizayaga FX Aguejouf O Desplat V Belon P Doutremepuich C 《World journal of gastroenterology : WJG》2007,13(38):5065-5070
AIM To study the mechanism involved in the potentially beneficial effect of ultra low dose aspirin (ULDA) in prehepatic portal hypertension, rats were pretreated with selective COX 1 or 2 inhibitors (SC-560 or NS-398 respectively), and subsequently injected with ULDA or placebo.METHODS Portal hypertension was induced by portal vein ligation. Platelet activity was investigated with an in-vivo model of laser induced thrombus production in mesenteric circulation and induced hemorrhagic time (IHT). Platelet aggregation induced by ADP and dosing of prostanoid products 6-keto-PGF1α, TXB2, PGE2 and LTB4 were also performed.RESULTS The portal hypertensive group receiving a placebo showed a decreased in vivo platelet activity with prolonged IHT, an effect that was normalized by ULDA. SC-560 induced a mild antithrombotic effect in the normal rats, and an unmodified effect of ULDA. NS-398 had a mild prothrombotic action in portal hypertensive rats, similar to ULDA, but inhibited a further effect when ULDA was added. An increased 6-keto-PGF1α was observed in portal hypertensive group that was normalised after ULDA administration. TXA2 level after ULDA, remained unchanged.CONCLUSION These results suggest that the effect of ULDA on platelet activity in portal hypertensive rats,could act through a COX 2 pathway more than the COX 1,predominant for aspirin at higher doses. 相似文献
96.
Soodi M Sharifzadeh M Naghdi N Ostad N Abdollahi M Roghani A 《Journal of neuroscience research》2007,85(14):3183-3192
Chronic lead exposure during development is known to produce learning deficits. In the present study, we investigated the effects of developmental exposure to lead on spatial memory, as shown in the Morris water maze, and on expression of inducible cyclooxygenase-2 protein in the hippocampi of male rats. Rats were separated into four groups according to which concentration of lead acetate at which developmental stage they were exposed. One group was exposed maternally to lead acetate at a concentration of 250 parts per million (ppm), one group was exposed continuously to 250 ppm lead, one group was exposed maternally to 750 ppm lead, and one group was exposed continuously to 750 ppm lead. Increases were observed in both average escape latency and traveled distance of the rats in the maternally and continuously 750 ppm lead-exposed groups, indicating significant impairment of spatial memory. Quantitative immunostaining analysis by optical density measurement of brain sections from rats in all lead-exposed groups revealed a significant reduction (P < 0.001) in the intensity of cyclooxygenase-2 immunoreactivity in the Ammon's horn region 1 (CA1) and the dentate gyrus areas of the hippocampus. This reduction was concentration-dependent, with the maximum reduction observed in rats exposed to 750 ppm lead. Taken together, these findings suggest that exposure to lead causes spatial memory deficits in male rats and a significant reduction in cyclooxygenase-2 immunoreactivity in the CA1 and dentate gyrus areas. 相似文献
97.
Okayama M Hayashi S Aoi Y Nishio H Kato S Takeuchi K 《Digestive diseases and sciences》2007,52(9):2095-2103
We examined the effect of cyclooxygenase (COX) inhibitors on dextran sulfate sodium (DSS)-induced ulcerative colitis in rats
and investigated the role of COX isozymes in the pathogenesis of this model. Experimental colitis was induced by treatment
with 2.5% DSS in drinking water for 6 days. Indomethacin (a nonselective COX inhibitor), SC-560 (a selective COX-1 inhibitor),
or celecoxib (a selective COX-2 inhibitor) was given PO twice daily for 6 days, during the first 3 or last 3 days of the experimental
period. Daily treatment with 2.5% DSS for 6 days caused damage to the colon, with a decrease in body weight gain and colon
length as well as an increase of myeloperoxidase (MPO) activity. All COX inhibitors given for 6 days significantly worsened
the severity of DSS-induced colonic damage with increased MPO activity. The aggravation was also observed by SC-560 given
for the first 3 days or by celecoxib given for the last 3 days. The expression of COX-2 mRNA in the colon was upregulated
on day 3 during DSS treatment, with significant increase of prostaglandin E2 PGE2 production. The PGE2 content on day 3 during DSS treatment was inhibited by both indomethacin and SC-560, but not by celecoxib; on day 6 it was
suppressed by both indomethacin and celecoxib, but not SC-560. These results suggest that endogenous prostaglandins (PGs)
afford protection against colonic ulceration, yet the COX isozyme responsible for the production of PGs differs depending
on the stage of ulceration; COX-1 in the early stage and COX-2 in the late stage. 相似文献
98.
Laleman W Van Landeghem L Van der Elst I Zeegers M Fevery J Nevens F 《Gastroenterology》2007,132(2):709-719
BACKGROUND & AIMS: We studied whether administration of nitroflurbiprofen (HCT-1026), a cyclooxygenase inhibitor with nitric oxide (NO)-donating properties, modulates the increased intrahepatic vascular tone in portal hypertensive cirrhotic rats. METHODS: In vivo hemodynamic measurements (n = 8/condition) and evaluation of the increased intrahepatic resistance by in situ perfusion (n = 5/condition) were performed in rats with thioacetamide-induced cirrhosis that received either nitroflurbiprofen (45 mg/kg), flurbiprofen (30 mg/kg, equimolar concentration to nitroflurbiprofen), or vehicle by intraperitoneal injection 24 hours and 1 hour prior to the measurements. Additionally, we evaluated the effect of acute administration of both drugs (250 micromol/L) on the intrahepatic vascular tone in the in situ perfused cirrhotic rat liver (endothelial dysfunction and hyperresponsiveness to methoxamine) and on hepatic stellate cell contraction in vitro. Typical systemic adverse effects of nonsteroidal anti-inflammatory drugs, such as gastrointestinal ulceration, renal insufficiency, and hepatotoxicity, were actively explored. RESULTS: In vivo, nitroflurbiprofen and flurbiprofen equally decreased portal pressure (8 +/- 0.8 and 8.4 +/- 0.1 mm Hg, respectively, vs 11.8 +/- 0.6 mm Hg) and reduced the total intrahepatic vascular resistance. Systemic hypotension was not aggravated in the different treatment groups (P = .291). In the perfused cirrhotic liver, both drugs improved endothelial dysfunction and hyperresponsiveness. This was associated with a decreased hepatic thromboxane A(2)-production and an increased intrahepatic nitrate/nitrite level. In vitro, nitroflurbiprofen, more than flurbiprofen, decreased hepatic stellate cells contraction. Flurbiprofen-treated rats showed severe gastrointestinal ulcerations (bleeding in 3/8 rats) and nefrotoxicity, which was not observed in nitroflurbiprofen-treated cirrhotic rats. CONCLUSIONS: Treatment with nitroflurbiprofen, an NO-releasing cyclooxygenase inhibitor, improves portal hypertension without major adverse effects in thioacetamide-induced cirrhotic rats by attenuating intrahepatic vascular resistance, endothelial dysfunction, and hepatic hyperreactivity to vasoconstrictors. 相似文献
99.
Wan‐Lin Wu Ling‐Jun Ho Deh‐Ming Chang Chen‐Hung Chen Jenn‐Haung Lai 《European journal of immunology》2009,39(12):3413-3422
A term “bone‐breaking fever” is used in Chinese medicine to describe the symptoms of patients infected with dengue virus (DV). We examined the significance of the COX‐prostaglandin pathway in human DC infected by DV. We show that DV infection induced the expression of COX‐2 and the production of prostaglandin E2 (PGE2) in DC, and stimulated the DNA binding of NF‐κB and the kinase activity of both IκBα kinase (IKK) α and β. DV infection also activated MAPK and AP‐1 signaling. Both IκBα kinase‐NF‐κB and MAPK‐AP‐1 were upstream of COX‐2 activation. Our investigation into the significance of COX‐2‐PGE2 pathway also revealed that DV infection enhances DC migration by inducing CC chemokine receptor 7 (CCR7) expression, and that blocking COX‐2 or MAPK activity suppresses DV‐induced DC migration. Our data also suggest that PGE2 can induce CCR7 expression on DC and that antagonists of the PGE2 receptors EP2 and EP4 suppress DV‐induced DC migration. We further show that the increased CCR7 expression was observed in both DV‐infected and bystander DC, suggesting the presence of secondary effects in inducing CCR7 expression. Collectively, this study reveals not only the pathways involved in COX‐2 synthesis in DV‐infected DC but also the autocrine action of PGE2 on the migration of DV‐infected DC. 相似文献