全文获取类型
收费全文 | 5940篇 |
免费 | 248篇 |
国内免费 | 57篇 |
专业分类
耳鼻咽喉 | 69篇 |
儿科学 | 112篇 |
妇产科学 | 82篇 |
基础医学 | 950篇 |
口腔科学 | 116篇 |
临床医学 | 340篇 |
内科学 | 1705篇 |
皮肤病学 | 58篇 |
神经病学 | 417篇 |
特种医学 | 152篇 |
外科学 | 803篇 |
综合类 | 40篇 |
预防医学 | 233篇 |
眼科学 | 39篇 |
药学 | 399篇 |
中国医学 | 8篇 |
肿瘤学 | 722篇 |
出版年
2023年 | 20篇 |
2022年 | 61篇 |
2021年 | 122篇 |
2020年 | 45篇 |
2019年 | 62篇 |
2018年 | 85篇 |
2017年 | 59篇 |
2016年 | 112篇 |
2015年 | 88篇 |
2014年 | 124篇 |
2013年 | 154篇 |
2012年 | 274篇 |
2011年 | 294篇 |
2010年 | 171篇 |
2009年 | 165篇 |
2008年 | 349篇 |
2007年 | 400篇 |
2006年 | 353篇 |
2005年 | 346篇 |
2004年 | 373篇 |
2003年 | 341篇 |
2002年 | 355篇 |
2001年 | 169篇 |
2000年 | 202篇 |
1999年 | 151篇 |
1998年 | 78篇 |
1997年 | 74篇 |
1996年 | 81篇 |
1995年 | 81篇 |
1994年 | 66篇 |
1993年 | 61篇 |
1992年 | 91篇 |
1991年 | 104篇 |
1990年 | 97篇 |
1989年 | 79篇 |
1988年 | 90篇 |
1987年 | 62篇 |
1986年 | 44篇 |
1985年 | 66篇 |
1984年 | 38篇 |
1983年 | 28篇 |
1982年 | 23篇 |
1981年 | 19篇 |
1980年 | 13篇 |
1979年 | 31篇 |
1974年 | 15篇 |
1973年 | 12篇 |
1970年 | 11篇 |
1968年 | 12篇 |
1967年 | 12篇 |
排序方式: 共有6245条查询结果,搜索用时 31 毫秒
21.
The present study was designed to investigate whether or not arginine vasopressin (AVP) is released from magnocellular neurons within the median eminence (ME) in vivo. Urethane-anesthetized adult male Wistar rats were equipped with a microdialysis probe aimed at the supraoptic (SON) or paraventricular nucleus (PVN), a push-pull perfusion probe resting in the ME, and a blood microdialysis probe within the jugular vein. Dialysis of the SON (but not the PVN) with Ringer's solution containing 56 mmol l−1 K+ resulted in an increase in AVP release within the ME (to 492 ± 192% of release during basal conditions,P < 0.05) and into blood (to 138 ± 9%,P < 0.01) whereby the release probably occurred from axonal swellings and nerve terminals of supraoptic neurons which project through the internal zone of the ME to the posterior pituitary. The calculated amount of AVP released into the extracellular fluid of the ME was high enough (approximately 1 pg/μ1) to hypothesize that the neuropeptide could enter the portal blood capillaries in physiologically relevant concentrations. Taken together, the present study indicates that activation of magnocellular neurons is accompanied by release of AVP within the median eminence. We assume that AVP released in this way might mediate a communication between the hypothalamic-neurohypophysial system and the hypothalamic-pituitary-adrenal axis in response to selected stressful stimuli. 相似文献
22.
Y. Tsutsumi T. Kihira S. Tsunoda T. Kanamori S. Nakagawa T. Mayumi 《British journal of cancer》1995,71(5):963-968
This study was conducted to increase the anti-tumour potency and reduce the toxic side-effects of tumour necrosis factor alpha (TNF-alpha). Natural human TNF-alpha was chemically conjugated with monomethoxy polyethylene glycol (PEG) using succinimidyl coupling of lysine amino groups of TNF-alpha. The number-average molecular weight of PEG-modified TNF-alpha (PEG-TNF-alpha) increased with an increase in the reaction time and the initial molar ratio of PEG relative to TNF-alpha. The resulting modified TNF-alpha was separated into fractions of various molecular weights. The specific activity of separated PEG-TNF-alpha s relative to that of native TNF-alpha gradually decreased with an increase in the degree of PEG modification, but the plasma half-life was drastically increased with the increase in molecular weight of modified TNF-alpha. PEG-TNF-alpha s, in which 29% and 56% of lysine residues were coupled to PEG, had anti-tumour activity approximately 4 and 100 times greater than unmodified TNF-alpha in the murine Meth-A fibrosarcoma model. Extensive PEG modification did not increase its in vivo activity. A high dose of unmodified TNF-alpha induced toxic side-effects, but these were not observed with the modified TNF-alpha s. Optimal PEG modification of TNF-alpha markedly increased its bioavailability and may facilitate its potential anti-tumour therapeutic use. 相似文献
23.
Kenji Takahashi Toshikazu Kubo Kappei Kobayashi Jiro Imanishi Masaharu Tkigawa Yuji Arai Yasusuke Hirasawa 《Journal of orthopaedic research》1997,15(1):150-158
The present study investigated the influence of hydrostatic prssure on the exprssion of cytokines and heat shock protein 70 in a chondrocyte-like cell line. Chondrocyte-like cells (HCS-2/8) were exposed to hydrostatic pressur by a special pressure apparatus. Total RNA for cytokines (interleukin-1β, basic fibroblast growth factor, insulin-like growth factor-I, and transforming growth factor-β1) and for heat shock protein 70 was extracted and was analyzed by a polymerase chain reaction method and Northern blotting. An assay for incorporation of [35S]sulfate was performed to assess proteoglycan synthesis. The expression of transforming growth factor-β1 mRNA was enhanced after exposure to 5 Mpa of hydrostatic prssure and was reduced after 50 Mpa, whereas the expression of heat shock protein 70 was enhanced following exposure to 50 Mpa of hydrostatic pressure. The incorporation of [35S]sulfate into the cultured cells increased following exposure to 1-5 Mpa of hydrostatic pressure and decreased following 10-50 Mpa of pressure. These results suggest that hydrostatic pressure at physiologic levels enhances the expression of transforkming growth factor-β mRNA in addition to increasing proteoglycan synthesis in chondrocytes and that excessively high hydrostatic pressure reduces the expression of transforming growth factor-β1 mRNA and increases the expression of heat shock protein 79 mRNA while decreasing proteoglycan synthesis. 相似文献
24.
A 28-year-old woman with a left frontoparietal anaplastic astrocytoma was treated postoperatively with a combination of cisplatin and 1-(4-amino-2-methylpyrimidine-5-yl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU). The drugs were infused via the left supraophthalmic internal carotid artery in an attempt to avoid ocular toxicity. The patient subsequently developed blindness in the left eye and a right temporal hemianopsia from marked degeneration of the left optic nerve and tract. It is apparent that the placement of a catheter into the supraophthalmic carotid artery does not exclude visual complications. 相似文献
25.
隔离饲养及给药时刻对小鼠阿米卡星药物动力学的影响 总被引:1,自引:0,他引:1
目的:研究社会环境及给药时刻对小鼠阿米卡星代谢的影响。方法:小鼠按饲养环境;隔离饲养(I)或集体饲养(A)及给药时间:日中(D)及午液(N)随机分为:I-D,I-N,A-D,A-N4组,饲养4周后于D(13:00)或N(01:00)sc阿米卡星15mg.kg^-1测定给药后血浆浓度,以开放一室模型拟合计算有关药代动力学参数,结果:A-N组阿米卡星清除较率A-D及I-N组增大,血浆半衰期变短,0-1 相似文献
26.
Granulocyte-macrophage colony stimulating factor (GM-CSF) modulates various functions of monocytes/ macrophages including antigen-presenting capacity. Recently it was found that astrocytes produce GM-CSF in the central nervous system (CNS) and that GM-CSF can induce proliferation and morphological changes of microglia. Here we show that GM-CSF can down regulate the interferon-γ-mediated induction of major histocompatibility complex (MHC) class II antigens in microglia, but not in astrocytes. GM-CSF pretreatment completely prevents myelin basic protein-specific T cell proliferation induced by microglia but not astrocytes. GM-CSF did not affect the cell surface expression on microglia of either MHC class I or cell adhesion molecules. The inhibition of microglial MHC class II expression and antigen-presenting function is specific for GM-CSF, as treatment with a different CSF (interleukin-3) did not modulate microglial phenotype or functional capacity. These data suggest that GM-CSF might be involved in the regulation of immune responses within the central nervous system. 相似文献
27.
M. Kamberi T. Kotegawa K. Tsutsumi K. Nakamura S. Nakano 《European journal of clinical pharmacology》1998,54(8):633-637
Objective: To investigate the effect of acidification and alkalinization on the pharmacokinetics of sparfloxacin in healthy subjects.
Methods: A single 200-mg oral dose of sparfloxacin was given to nine healthy Japanese volunteers on three separate occasions under
different conditions of urinary pH. Acidic and alkaline conditions were achieved by repeated oral doses of ammonium chloride
and sodium bicarbonate, respectively. The concentrations of sparfloxacin and its metabolite in plasma and urine were determined
by high-performance liquid chromatography assays.
Results: The difference between treatments for Cmax, AUC∞, and CL · f−1 were found to be significant. The relative bioavailability of sparfloxacin was 84.4% and 122.3% after ammonium chloride and
sodium bicarbonate treatments, respectively. The amount of unchanged sparfloxacin in urine samples collected 0–48 h after
sparfloxacin administration represented 10.1% of the dose in the control, 14.3% of the dose in urine acidification and 8.4%
of the dose with alkalinization of urine. Renal clearance was found to depend on urinary pH. However, the plasma elimination
and the metabolism of sparfloxacin were not significantly altered by acidification or alkalinization of the urine.
Conclusion: The urinary pH dependence of the renal clearance of sparfloxacin will be of minor clinical importance with regard to the
low contribution of renal excretion to the overall elimination of sparfloxacin. On the other hand, the alteration in the environmental
pH in the gastrointestinal tract, produced by the concomitant ingestion of ammonium chloride or sodium bicarbonate, influences
the absorption and bioavailability of sparfloxacin. This effect is likely to be clinically significant.
Received: 18 March 1998 / Accepted in revised form: 1 July 1998 相似文献
28.
29.
Eimoto Hiroyuki; Tsutsumi Masahiro; Nakajima Akira; Yamamoto Kazuhiko; Takashima Yokashima; Maruyama Hiroshi; Konishi Yoichi 《Carcinogenesis》1988,9(12):2325-2327
Expression of glutathione S-transferase placental form (GST-)in human lung carcinoma tissue taken at autopsy or biopsy wasinvestigated immunohistochemically. All of 34 cases of squamouscell carcinomas, including poorly, moderatelyand well-differentiatedexamples were shown to stain positively for GST-. Poorly differentiatedadenocarcinomas were, however, negatively stained (0/5 cases),while moderately and well differentiated adenocarcinomas werefound tostain with GST- at rates of 69% (9/13 cases) and 71%(5/7 cases), respectively. Six cases of small cell carcinomasexamined were all negative. The results indicate that GST- maybe a useful marker fornon-small cell type lung cancer, especiallysquamous cell carcinoma which is in agreement with findingsfor rat lung neoplastic lesions reported previously. 相似文献
30.
Possible involvement of arachidonic acid metabolism in phenobarbital promotion of hepatocarcinogenesis 总被引:8,自引:4,他引:4
Denda Ayumi; Ura Hitoshi; Tsujiuchi Toshifumi; Masahiro Tsutsumi; Eimoto Hiroyuki; Takashima Yoshiharu; Kitazawa Shunji; Kinugasa Tetsuo; Konishi Yoich 《Carcinogenesis》1989,10(10):1929-1935
The effects of inhibitors of arachidonic acid metabolism andantioxidants on the rat liver tumor promotion activity of phenobarbital(PB) were assessed using the enzyme-altered focus as the end-pointlesion. Fischer 344 male rats were initiated with N-nitrosodiethylamine(200 mg/kg) and then divided into five groups placed on basaldiet, diet containing 0.05% PB, diet containing 0.05% PB plus0.75%, 1% or 1.5% levels of various inhibitors of arachidonicacid metabolism or antioxidants, or diet containing 1% or 1.5%inhibitors or antioxidants alone for 10 weeks, and then killed.-Bromo phenacyl bromide, an inhibitor of phospholipase A2 significantly inhibited the promotion activity of PB at dose levelsof 0.75% and 1.5%, reaching plateau at 0.75%. Both quercetin,an inhibitor of lipoxygenase, and morin, a dual inhibitor oflipoxygenase-cyclooxygenase, significantly reduced the promotionactivity of PB at the 1.5% but not 0.75% dose levels. Moreover,acetylsalicylic acid, an inhibitor of cyclooxygenase dose-dependentlyinhibited the promotion activity of PB. Among the antioxidantsinvestigated, vitamin E did not affect, but n-propyl gallateand ethoxyquin exerted a dose-dependent inhibition of PB promotion.These results are strongly suggestive of an involvement of phospholipaseA2 lipoxygenase and cyclooxygenase arachidonic acid metabolicpathways in the mechanisms underlying PB enhancement of hepatocarcinogenesis. 相似文献