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   7839篇
  免费   1315篇
  国内免费   827篇
  2023年   219篇
  2022年   202篇
  2021年   266篇
  2020年   356篇
  2019年   377篇
  2018年   330篇
  2017年   381篇
  2016年   362篇
  2015年   321篇
  2014年   418篇
  2013年   559篇
  2012年   286篇
  2011年   355篇
  2010年   329篇
  2009年   437篇
  2008年   433篇
  2007年   484篇
  2006年   402篇
  2005年   397篇
  2004年   304篇
  2003年   263篇
  2002年   253篇
  2001年   186篇
  2000年   158篇
  1999年   138篇
  1998年   132篇
  1997年   105篇
  1996年   109篇
  1995年   117篇
  1994年   102篇
  1993年   118篇
  1992年   101篇
  1991年   78篇
  1990年   66篇
  1989年   77篇
  1988年   52篇
  1987年   46篇
  1986年   60篇
  1985年   84篇
  1984年   81篇
  1983年   64篇
  1982年   88篇
  1981年   72篇
  1980年   55篇
  1979年   53篇
  1978年   20篇
  1977年   16篇
  1975年   11篇
  1974年   11篇
  1973年   16篇
排序方式: 共有9981条查询结果,搜索用时 15 毫秒
1.
目的:探讨肝癌乙型肝炎病毒(HBV)感染患者根治性切除术后采用恩替卡韦抗病毒治疗的临床疗效及安全性。方法:收集2015年1月-2017年8月在我院行根治性切除术的肝癌HBV感染患者279例为研究对象,以血清HBV-DNA载量10~5 copies/ml为界限,分为高病毒复制组128例,低病毒复制组151例,按照随机数字表法将高病毒复制组分为高-治疗组64例、高-对照组64例,将低病毒复制组分为低-治疗组76例、低-对照组75例。高-治疗组和低-治疗组术后给予恩替卡韦0.5 mg/d,高-对照组和低-对照组未行抗病毒治疗。比较手术前、术后7 d各组的血清HBV-DNA水平,血清白蛋白(ALB)、谷丙转氨酶(ALT)、前白蛋白(PA),以及术后并发症的发生情况。结果:高-治疗组、高-对照组、低-治疗组、低-对照组术后血清ALB、PA均较治疗前降低,血清ALT均较治疗前升高,且高-治疗组或低-治疗组术后血清ALB、PA均高于高-对照组或低-对照组,血清ALT水平均低于高-对照组或低-对照组,差异均有统计学意义(P0.05);高-治疗组或低-治疗组术后血清HBV-DNA水平均低于治疗前,且均低于同期高-对照组或低-对照组,差异均有统计学意义(P0.05)。高-治疗组与高-对照组、低-治疗组与低-对照组患者术后并发症发生率均无统计学差异(P0.05)。结论:恩替卡韦能显著改善肝癌HBV感染患者术后的血清HBV-DNA载量水平和肝功能,安全性高,值得临床推广。  相似文献   
2.
目的:探讨曲美他嗪或生脉饮分别与黄芪注射液联用治疗急性病毒性心肌炎(AVMC)的临床疗效。方法:选取2013年4月~2016年4月我院收治的AVMC患者140例,按随机数字表法分为对照组(n=45)、曲黄组(n=46)及生黄组(n=49)。对照组患者给予常规药物治疗,曲黄组在对照组的基础上给予曲美他嗪联合黄芪注射液治疗,生黄组在对照组的基础上给予生脉饮联合黄芪注射液治疗。比较三组患者中血清肌酸磷酸激酶同工酶(CK-MB)、心肌钙蛋白I(cTnI)水平、心电图指标、临床总有效率、临床症状改善及不良反应情况。结果:治疗后,曲黄组和生黄组总有效率均显高于对照组,曲黄组总有效率高于生黄组(P0.05)。曲黄组和生黄组患者的心悸和胸痛发生率低于对照组,差异具有统计学意义(P0.05)。曲黄组和生黄组患者血清CK-MB、cTnI水平低于对照组,且曲黄组低于生黄组(P0.05)。曲黄组患者房室传导阻滞、ST-T变化、室性期前收缩发生率低于对照组(P0.05)。三组患者不良反应发生率比较无统计学差异(P0.05)。结论:曲美他嗪联合黄芪注射液治疗AVCM的总有效率高于生脉饮联合黄芪注射液治疗,降低心肌损伤程度,改善临床症状,无严重不良反应,值得临床推广应用。  相似文献   
3.
银杏内生菌Chaetomium globosum ZY-22次生代谢产物分离鉴定   总被引:2,自引:0,他引:2  
采用柱层析方法从银杏叶内生真菌Chaetomium globosum ZY-22的培养菌丝体提取物中分离得到脑苷脂B(1)、脑苷脂C(2)、尿囊素(3)、9(11)-去氢麦角甾醇过氧化物(4)以及4,6,8,22-四烯-3-酮-麦角甾烷(5)和球毛壳甲素(6)共6个次生代谢物;经波谱分析确定了6个化合物的结构,其中脑苷脂B、脑苷脂C和尿囊素是首次从内生真菌中得到;海虾致死试验结果显示,化合物1~6在10 μg/mL浓度下对丰年虾的致死率分别为1.6%、4.2%、7.4%、16.9%、12.8%、83.6%、表明球毛壳甲素对海虾表现出很强的毒性作用.  相似文献   
4.
Extracts of Prunella vulgaris have been shown to exert antiestrogenic effects. To identify the compounds responsible for these actions, we isolated the constituents of P. vulgaris and tested their individual antiestrogenic effects. Rosmarinic acid, caffeic acid, ursolic acid (UA), oleanolic acid, hyperoside, rutin and betulinic acid (BA) were isolated from the flower stalks of P. vulgaris var. lilacina Nakai (Labiatae). Among these constituents, UA and BA showed significant antiestrogenic effects, measured as a decrease in the mRNA level of GREB1, an estrogen-responsive protein; the effects of BA were stronger than those of UA. UA and BA were capable of suppressing estrogen response element (ERE)-dependent luciferase activity and expression of estrogen-responsive genes in response to exposure to estradiol, further supporting the suppressive role of these compounds in estrogen-induced signaling. However, neither UA nor BA was capable of suppressing estrogen signaling in cells ectopically overexpressing estrogen receptor α (ERα). Furthermore, both mRNA and protein levels of ERα were reduced by treatment with UA or BA, suggesting that UA and BA inhibit estrogen signaling by suppressing the expression of ERα. Interestingly, both compounds enhanced prostate-specific antigen promoter activity. Collectively, these findings demonstrate that UA and BA are responsible for the antiestrogenic effects of P. vulgaris and suggest their potential use as therapeutic agents against estrogen-dependent tumors.  相似文献   
5.
6.
7.
E1 and E2 are two hepatitis C viral envelope glycoproteins that assemble into a heterodimer that is essential for membrane fusion and penetration into the target cell. Both extracellular and transmembrane (TM) glycoprotein domains contribute to this interaction, but study of TM–TM interactions has been limited because synthesis and structural characterization of these highly hydrophobic segments present significant challenges. In this NMR study, by successful expression and purification of the E2 transmembrane domain as a fusion construct we have determined the global fold and characterized backbone motions for this peptide incorporated in phospholipid micelles. Backbone resonance frequencies, relaxation rates and solvent exposure measurements concur in showing this domain to adopt a helical conformation, with two helical segments spanning residues 717–726 and 732–746 connected by an unstructured linker containing the charged residues D728 and R730 involved in E1 binding. Although this linker exhibits increased local motions on the ps timescale, the dominating contribution to its relaxation is the global tumbling motion with an estimated correlation time of 12.3 ns. The positioning of the helix–linker–helix architecture within the mixed micelle was established by paramagnetic NMR spectroscopy and phospholipid-peptide cross relaxation measurements. These indicate that while the helices traverse the hydrophobic interior of the micelle, the linker lies closer to the micelle perimeter to accommodate its charged residues. These results lay the groundwork for structure determination of the E1/E2 complex and a molecular understanding of glycoprotein heterodimerization.  相似文献   
8.
9.
10.
In this article, we discuss molecular mechanisms involved in the evolution of amygdala kindling and the episodic loss of response to pharmacological treatments during tolerance development. These phenomena allow us to consider how similar principles (in different neurochemical systems) could account for illness progression, cyclicity, and drug tolerance in affective disorders. We describe the phenomenon of amygdala-kindled seizures episodically breaking through effective daily pharmacotherapy with carbamazepine and valproate, suggesting that these observations could reflect the balance of pathological vs compensatory illness-induced changes in gene expression. Under certain circumstances, amygdala-kindled animals that were initially drug responsive can develop highly individualized patterns of seizure breakthroughs progressing toward a complete loss of drug efficacy. This initial drug efficacy may reflect the combination of drug-related exogenous neurochemical mechanisms and illness-induced endogenous compensatory mechanisms. However, we postulate that when seizures are inhibited, the endogenous illness-induced adaptations dissipate (the “time-off seizure” effect), leading to the re-emergence of seizures, a re-induction of a new, but diminished, set of endogenous compensatory mechanisms, and a temporary period of renewed drug efficacy. As this pattern repeats, an intermittent or cyclic response to the anticonvulsant treatment emerges, leading toward complete drug tolerance. We also postulate that the cyclic pattern accelerates over time because of both the failure of robust illness-induced endogenous adaptations to emerge and the progression in pathophysiological mechanisms (mediated by long-lasting changes in gene expression and their downstream consequences) as a result of repeated occurrences of seizures. In this seizure model, this pattern can be inhibited and drug responsivity can be temporarily reinstated by several manipulations, including lowering illness drive (decreasing the stimulation current.), increasing drug dosage, switching to a new drug that does not show crosstolerance to the original medication, or temporarily discontinuing treatment, allowing the illness to re-emerge in an unmedicated animal. Each of these variables is discussed in relation to the potential relevance to the emergence, progression, and suppression of individual patterns of episodic cyclicity in the recurrent affective disorders. A variety of clinical studies are outlined that specifically test the hypotheses derived from this formulation. Data from animal studies suggest that illness cyclicity can develop from the relative ratio between primary pathological processes and secondary endogenous adaptations (assisted by exogenous medications). If this proposition is verified, it further suggests that illness cyclicity is inherent to the neurobiological processes of episode emergence and amelioration, and one does not need to postulate a separate defect in the biological clock. The formulation predicts that early and aggressive long-term interventions may be optimal in order to prevent illness emergence and progression and its associated accumulating neurobiological, vulnerability factors.  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