全文获取类型
收费全文 | 9617篇 |
免费 | 404篇 |
国内免费 | 171篇 |
专业分类
耳鼻咽喉 | 71篇 |
儿科学 | 116篇 |
妇产科学 | 117篇 |
基础医学 | 1679篇 |
口腔科学 | 449篇 |
临床医学 | 415篇 |
内科学 | 1384篇 |
皮肤病学 | 50篇 |
神经病学 | 843篇 |
特种医学 | 173篇 |
外科学 | 1715篇 |
综合类 | 866篇 |
预防医学 | 470篇 |
眼科学 | 38篇 |
药学 | 1491篇 |
1篇 | |
中国医学 | 176篇 |
肿瘤学 | 138篇 |
出版年
2023年 | 54篇 |
2022年 | 90篇 |
2021年 | 143篇 |
2020年 | 135篇 |
2019年 | 137篇 |
2018年 | 163篇 |
2017年 | 159篇 |
2016年 | 174篇 |
2015年 | 210篇 |
2014年 | 401篇 |
2013年 | 445篇 |
2012年 | 363篇 |
2011年 | 394篇 |
2010年 | 298篇 |
2009年 | 427篇 |
2008年 | 456篇 |
2007年 | 458篇 |
2006年 | 433篇 |
2005年 | 422篇 |
2004年 | 298篇 |
2003年 | 305篇 |
2002年 | 258篇 |
2001年 | 247篇 |
2000年 | 253篇 |
1999年 | 282篇 |
1998年 | 239篇 |
1997年 | 239篇 |
1996年 | 201篇 |
1995年 | 233篇 |
1994年 | 244篇 |
1993年 | 192篇 |
1992年 | 183篇 |
1991年 | 138篇 |
1990年 | 148篇 |
1989年 | 127篇 |
1988年 | 107篇 |
1987年 | 150篇 |
1986年 | 113篇 |
1985年 | 122篇 |
1984年 | 95篇 |
1983年 | 55篇 |
1982年 | 77篇 |
1981年 | 61篇 |
1980年 | 60篇 |
1979年 | 54篇 |
1978年 | 54篇 |
1977年 | 54篇 |
1976年 | 45篇 |
1975年 | 32篇 |
1973年 | 36篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
961.
Giuseppina Martella Paola Bonsi Giuseppe Sciamanna Paola Platania Graziella Madeo Annalisa Tassone Dario Cuomo Antonio Pisani 《Epilepsia》2009,50(4):702-710
Purpose: We analyzed the effects of seletracetam (ucb 44212; SEL), a new antiepileptic drug candidate, in an in vitro model of epileptic activity. The activity of SEL was compared to the effects of levetiracetam (LEV; Keppra), in the same assays. Methods: Combined electrophysiologic and microfluorometric recordings were performed from layer V pyramidal neurons in rat cortical slices to study the effects of SEL on the paroxysmal depolarization shifts (PDSs), and the simultaneous elevations of intracellular Ca2+ concentration [Ca2+]i. Moreover, the involvement of high‐voltage activated Ca2+ currents (HVACCs) was investigated by means of patch‐clamp recordings from acutely dissociated pyramidal neurons. Results: SEL significantly reduced both the duration of PDSs (IC50 = 241.0 ± 21.7 nm ) as well as the number of action potentials per PDS (IC50 = 82.7 ± 9.7 nm ). In addition, SEL largely decreased the [Ca2+]i rise accompanying PDSs (up to 75% of control values, IC50 = 345.0 ± 15.0 nm ). Furthermore, SEL significantly reduced HVACCs in pyramidal neurons. This effect was mimicked by ω‐conotoxin GVIA and, to a lesser extent, by ω‐conotoxin MVIIC, blockers of N‐ and Q‐type HVACC, respectively. The combination of these two toxins occluded the action of SEL, suggesting that N‐type Ca2+ channels, and partly Q‐type subtypes are preferentially targeted. Conclusions: These results demonstrate a powerful inhibitory effect of SEL on epileptiform events in vitro. SEL showed a higher potency than LEV. The effective limitation of [Ca2+]i influx might be relevant for its antiepileptic efficacy and, more broadly, for pathologic processes involving neuronal [Ca2+]i overload. 相似文献
962.
Saori Morota Roland Mnsson Magnus J. Hansson Kazuhiko Kasuya Motohide Shimazu Erika Hasegawa Shigeru Yanagi Akibumi Omi Hiroyuki Uchino Eskil Elmr 《Experimental neurology》2009,218(2):353-362
Inhibition of mitochondrial permeability transition (mPT) has emerged as a promising approach for neuroprotection and development of well-tolerated mPT inhibitors with favorable blood-brain barrier penetration is highly warranted. In a recent study, 28 clinically available drugs with a common heterocyclic structure were identified as mPT inhibitors e.g. trifluoperazine, promethazine and nortriptyline. In addition, neuroprotection by structurally unrelated drugs e.g. neurosteroids, 4-hydroxy-tamoxifen and trimetazidine has been attributed to direct inhibition of mPT. The regulation of mPT is complex and highly dependent on the prevailing experimental conditions. Several features of mPT, such as swelling, depolarization or NADH oxidation, can also occur independently of the mPT phenomenon. Here, in isolated rodent brain-derived and human liver mitochondria, we re-evaluate drugs promoted as potent mPT inhibitors. We address the definition of an mPT inhibitor and present strategies to reliably detect mPT inhibition in vitro. Surprisingly, none of the 12 compounds tested displayed convincing mPT inhibition or effects comparable to cyclophilin D inhibition by the non-immunosuppressive cyclophilin inhibitor D-MeAla3-EtVal4-Cyclosporin (Debio 025). Propofol and 2-aminoethoxydiphenyl borate (2-APB) inhibited swelling in de-energized mitochondria but did not increase calcium retention capacity (CRC). Progesterone, trifluoperazine, allopregnanolone and 4-hydroxy-tamoxifen dose-dependently reduced CRC and respiratory control and were thus toxic rather than beneficial to mitochondrial function. Interestingly, topiramate increased CRC at high concentrations likely by a mechanism separate from direct mPT inhibition. We conclude that a clinically relevant mPT inhibitor should have a mitochondrial target and increase mitochondrial calcium retention at concentrations which can be translated to human use. 相似文献
963.
Calcium dysregulation induces apoptosis-inducing factor release: Cross-talk between PARP-1- and calpain- signaling pathways 总被引:1,自引:0,他引:1
Peter S. Vosler Dandan Sun Suping Wang Yanqin Gao Douglas B. Kintner Armando P. Signore Guodong Cao Jun Chen 《Experimental neurology》2009,218(2):213-220
Recent discoveries show that caspase-independent cell death pathways are a pervasive mechanism in neurodegenerative diseases, and apoptosis-inducing factor (AIF) is an important effector of this mode of neuronal death. There are currently two known mechanisms underlying AIF release following excitotoxic stress, PARP-1 and calpain. To test whether there is an interaction between PARP-1 and calpain in triggering AIF release, we used the NMDA toxicity model in rat primary cortical neurons. Exposure to NMDA resulted in AIF truncation and nuclear translocation, and shRNA-mediated knockdown of AIF resulted in neuroprotection. Both calpain and PARP-1 are involved with AIF processing as AIF truncation, nuclear translocation and neuronal death were attenuated by calpain inhibition using adeno-associated virus-mediated overexpression of the endogenous calpain inhibitor, calpastatin, or treatment with the PARP-1 inhibitor 3-ABA. Activation of PARP-1 is necessary for calpain activation as PARP-1 inhibition blocked mitochondrial calpain activation. Finally, NMDA toxicity induces mitochondrial Ca2+ dysregulation in a PARP-1 dependent manner. Thus, PARP-1 and mitochondrial calpain activation are linked via PARP-1-induced alterations in mitochondrial Ca2+ homeostasis. Collectively, these findings link the two seemingly independent mechanisms triggering AIF-induced neuronal death. 相似文献
964.
Knijn N Tol J Koopman M Werter MJ Imholz AL Valster FA Mol L Vincent AD Teerenstra S Punt CJ 《European journal of cancer (Oxford, England : 1990)》2011,47(3):369-374
Background
Peripheral sensory neurotoxicity is a frequent and potentially debilitating side effect of oxaliplatin treatment. Calcium and magnesium (Ca/Mg) infusions are frequently used to prevent this toxicity. However, concerns about a negative impact of Ca/Mg infusions on outcome have been raised. We retrospectively assessed the effect of Ca/Mg infusions on the incidence of neurotoxicity and on clinical outcome in advanced colorectal cancer (ACC) patients treated in the phase III CAIRO2 study.Materials and methods
Seven hundred and fifty five previously untreated ACC patients were randomised between treatment with capecitabine, oxaliplatin and bevacizumab or the same combination with the addition of cetuximab. Patients were retrospectively divided into two groups: patients in the Ca/Mg+ group received Ca/Mg at least during their first treatment cycle, and patients in the Ca/Mg- group did not.Results
Seven hundred and thirty two patients were evaluable for this analysis. The Ca/Mg+ group consisted of 551 patients, the Ca/Mg- group consisted of 181 patients. The incidence of all grade neurotoxicity in the Ca/Mg+ group and the Ca/Mg- group was 85% and 92%, respectively (p = 0.02), and the incidence of grade ? 2 neurotoxicity was 40% and 45%, respectively (p = 0.22). The median PFS in the Ca/Mg+ versus Ca/Mg- group was 10.1 versus 10.7 months (p = 0.92), the median OS was 19.8 versus 20.7 months (p = 0.10), and the response rate was 43.1% versus 50% (p = 0.11), respectively.Conclusions
In this largest retrospective analysis to date we observed that Ca/Mg infusions significantly reduced all grade oxaliplatin-related neurotoxicity. Ca/Mg infusions did not affect the clinical efficacy of treatment. 相似文献965.
目的:对慢性无窦道型根尖周炎进行一次法和多次法根管治疗,观察比较两者的临床疗效.方法:选择诊断为慢性无窦道型根尖周炎需行根管治疗的单根患牙150例,随机分为一次法(观察组)和多次法(对照组)两组各75例.一次法组在根管预备、冲洗后直接行根管充填;多次法组在根管预备后根管内封入Ca(OH)2尖,2周后再行报管充填.观察2... 相似文献
966.
目的建立测定血清中阿托伐他汀钙浓度的高效液相色谱法。方法色谱柱为Diamonsil C18柱(250mm×4.6 mm,5μm),乙腈-醋酸铵(冰醋酸调节pH至4.0)(50︰50)作流动相,流速1.0 ml.min-1,室温,以丹皮酚作为内标物,检测波长246 nm。结果在0.25~25μg.ml-1范围内,阿托伐他汀钙与内标物丹皮酚的峰面积比与阿托伐他汀钙浓度线性关系良好,r=0.9951(n=7),平均回收率为89.4%,日内RSD≤3.01%(n=3),日间RSD≤5.73%(n=3)。结论本法简便、快捷、选择性高,适用于阿托伐他汀钙的常规分析。 相似文献
967.
红花注射液对大鼠周围神经缺血再灌注损伤的保护作用及其机制研究 总被引:1,自引:0,他引:1
目的:研究红花注射液对大鼠周围神经缺血再灌注(IR)损伤的保护作用及其机制。方法:实验分为6组,即对照(等容生理盐水)、模型(等容生理盐水)、甘露醇(5mL.kg-1)和红花注射液高、中、低剂量组(32、16、8mL.kg-1),iv给药。阻断髂总动脉、髂内动脉和髂外动脉6h,复制周围神经IR模型。观察大鼠肢体功能,进行神经电生理检查,并检测坐骨神经组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、钙离子和肿瘤坏死因子-α(TNF-α)的水平。结果:与模型组比较,红花注射液高、中剂量组肢体功能评分和MDA水平显著降低,SOD活性显著升高(P<0.01或P<0.05);红花注射液高剂量组TNF-α和潜伏期显著下降,传导速度和波幅显著增加(P<0.01或P<0.05)。结论:红花注射液对周围神经IR损伤具有保护作用,其作用机制可能与抑制氧化应激、钙超载和炎症反应有关。 相似文献
968.
目的:观察氢氧化钙糊剂、替硝唑粉联合牙胶进行根管充填的疗效。方法:将126例患者的180颗患牙随机分为观察组与对根管照。组比,各较920组颗的牙充,对填照效组果采。用结根果管:观糊察剂组加与牙对胶照充组填的根超管充,观填察、欠组充将填氢、氧适化充填钙效糊果剂比和较替,硝差唑异粉无以统2计∶1学的意比义例(调P>配0好.0后5)加。牙但胶治充疗后填7d,观察组的急性反应发生率明显低于对照组,差异有统计学意义(P<0.05)。随访1年,观察组充填有效率明显高于对照组,差异有统计学意义(P<0.05)。观察组急慢性牙髓炎充填有效率、急慢性根尖周炎充填有效率分别明显高于对照组,差异均有统计学意义(P<0.05)。结论:氢氧化钙糊剂、替硝唑粉联合牙胶根管充填效果好,值得临床推广。 相似文献
969.
目的:观察硝苯地平联合贝那普利治疗糖尿病肾病的临床疗效。方法:将98例糖尿病肾病患者随机均分为2组,观察组49例采用硝苯地平联合贝那普利治疗,对照组49例仅采用硝苯地平治疗,比较2组的临床疗效和收缩压/舒张压(SBP/DBP)、空腹血糖(FBG)、24h尿α1-微球蛋白(α1-MG)和尿微量白蛋白(mAlb)水平的变化。结果:观察组的总有效率明显高于对照组(P<0.05)。与治疗前比较,2组治疗后SBP、DBP、FBG、α1-MG和mAlb水平均明显下降(P<0.05)。观察组治疗后α1-MG和mAlb水平均明显低于对照组(P<0.05),但FBG和SBP、DBP水平比较,差异均无统计学意义(P>0.05)。结论:硝苯地平联合贝那普利治疗糖尿病肾病能够明显提高临床疗效,降低血糖、血压和蛋白尿,减少对肾脏的损伤。 相似文献
970.