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排序方式: 共有228条查询结果,搜索用时 62 毫秒
1.
K Nakagawa T Tamura S Negoro S Kudoh N Yamamoto N Yamamoto K Takeda H Swaisland I Nakatani M Hirose R-P Dong M Fukuoka 《Annals of oncology》2003,14(6):922-930
BACKGROUND: This phase I dose-escalating study investigated the tolerability and toxicity of the selective epidermal growth factor receptor tyrosine kinase inhibitor gefitinib ('Iressa', ZD1839) in Japanese patients with solid tumors. Thirty-one patients were included. PATIENTS AND METHODS: Patients initially received a single oral dose of gefitinib followed by 10-14 days of observation. Oral gefitinib was subsequently administered on 14 consecutive days, every 28 days. Dose escalation was from 50 mg/day to a maximum of 925 mg/day or dose-limiting toxicity (DLT). RESULTS: Most adverse events were mild (grade 1/2); the most frequent were an acne-like rash and gastrointestinal effects. Two of six patients at 700 mg/day had DLT; no further dose escalation occurred. C(max) was reached within 3-7 h and exposure to gefitinib increased with dose. Mean terminal half-life following multiple dosing was 50.1 h (range 27.8-79.7 h). A partial response (duration 35-361 days) was observed in five of the 23 patients with non-small-cell lung cancer over a range of doses (225-700 mg/day), and seven patients with a range of tumors had disease stabilization (duration 40-127 days). CONCLUSIONS: In conclusion, gefitinib showed a favorable tolerability profile in Japanese patients. The safety profile, pharmacokinetic parameters and antitumor activity observed in our study are comparable to those observed in patients from the USA and Europe. 相似文献
2.
Clinical evaluation of ZD6474, an orally active inhibitor of VEGF and EGF receptor signaling, in patients with solid, malignant tumors. 总被引:7,自引:0,他引:7
S N Holden S G Eckhardt R Basser R de Boer D Rischin M Green M A Rosenthal C Wheeler A Barge H I Hurwitz 《Annals of oncology》2005,16(8):1391-1397
BACKGROUND: ZD6474 selectively inhibits the tyrosine kinase activity of vascular endothelial growth factor receptor and epidermal growth factor receptor. The safety, tolerability and pharmacokinetics of ZD6474 were assessed in a phase I dose-escalation study of patients with advanced solid tumors. PATIENTS AND METHODS: Adult patients with tumors refractory to standard treatments received once-daily oral ZD6474 (50-600 mg) in 28-day cycles, until disease progression or unacceptable toxicity was observed. RESULTS: Seventy-seven patients were treated at doses of 50 mg (n=9), 100 mg (n=19), 200 mg (n=8), 300 mg (n=25), 500 mg (n=8), and 600 mg (n=8). Adverse events were generally mild, and the most common dose-limiting toxicities (DLT) were diarrhea (n=4), hypertension (n=4), and rash (n=3). The incidence of most adverse events appeared to be dose-dependant. In the 500 mg/day cohort, 3/8 patients experienced DLT and this dose was therefore considered to exceed the maximum tolerated dose. Pharmacokinetic analysis confirmed that ZD6474 was suitable for once-daily oral dosing. CONCLUSIONS: Once-daily oral dosing of ZD6474 at 300 mg/day is generally well tolerated in patients with advanced solid tumors, and this dose is being investigated in phase II trials. 相似文献
3.
4.
Yu Chen Chun Lin Ying Tang Ai-Qin Chen Cui-Ying Liu Da-Li Lu 《World journal of gastroenterology : WJG》2014,20(8):2091-2097
AIM:To investigate the effects of ZD 7288,a hyperpolarization-activated cyclic nucleotide-gated(HCN)channel blocker,on rats with chronic visceral pain.METHODS:Rats with visceral hypersensitivity were generated using neonatal colon irritation during postnatal days 8-15 as described previously.Visceral hypersensitivity was evaluated using electromyographic(EMG)responses of abdominal external oblique muscles to 20-80 mmHg colorectal distentions(CRD).Abdominal withdrawal reflex(AWR)scores and pain thresholds were also detected in adult rats.Different doses of ZD7288(25,50,and 100 nmol/L)were intrathecally administered in rats to study the role of spinal HCN channel in chronic visceral hypersensitivity.RESULTS:EMG responses to 20-80 mmHg CRD and AWR scores under 20-60 mmHg CRD significantly increased in rats with visceral hypersensitivity compared to control rats(P<0.05).The pain threshold in rats with visceral hypersensitivity significantly decreased compared to control rats(P<0.05).Treatment with50-100 nmol/L ZD 7288 significantly inhibited EMG responses(16%-62%,80-20 mmHg CRD,P<0.05)and AWR scores(24%-37%,40-20 mmHg CRD,P<0.05;12%-61%,80-20 mmHg CRD,P<0.05,respectively),and significantly increased pain thresholds(32%-77%,P<0.05).CONCLUSION:Spinal HCN channels may play an important role in chronic visceral hypersensitivity. 相似文献
5.
Hippocampal theta rhythm has been associated with a number of behavioral processes, including learning and memory, spatial behavior, sensorimotor integration and affective responses. Suppression of hippocampal theta frequency has been shown to be a reliable neurophysiological signature of anxiolytic drug action in tests using known anxiolytic drugs (i.e., correlational evidence), but only one study to date (Yeung et al. ( 2012 ) Neuropharmacology 62:155–160) has shown that a drug with no known effect on either hippocampal theta or anxiety can in fact separately suppress hippocampal theta and anxiety in behavioral tests (i.e., prima facie evidence). Here, we attempt a further critical test of the hippocampal theta model by performing intrahippocampal administrations of the Ih blocker ZD7288, which is known to disrupt theta frequency subthreshold oscillations and resonance at the membrane level but is not known to have anxiolytic action. Intrahippocampal microinfusions of ZD7288 at high (15 µg), but not low (1 µg) doses slowed brainstem‐evoked hippocampal theta responses in the urethane anesthetized rat, and more importantly, promoted anxiolytic action in freely behaving rats in the elevated plus maze. Taken together with our previous demonstration, these data provide converging, prima facie evidence of the validity of the theta suppression model. © 2012 Wiley Periodicals, Inc. 相似文献
6.
观察超极化激活环核苷酸门控阳离子通道(HCN通道)的特异性阻断剂ZD7288对急性内脏痛大鼠痛觉敏化的影响。方法:选用成年雄性SD大鼠,通过结肠内注射1%醋酸1mL,建立急性内脏痛模型;免疫组织化学法检测HCN2在模型大鼠腰骶段背根神经节及胸腰段与腰骶段脊髓背角的表达;通过腹壁撤退反射评分和腹外斜肌放电测量,观察模型大鼠鞘内分别给予50与100nmol/LZD7288后内脏痛觉敏化是否发生改变。结果:HCN2在模型大鼠腰骶段背根神经节及胸腰段与腰骶段脊髓背角的表达均较对照大鼠增强(P〈0.05)。鞘内注射50~100nmol/LZD7288可以剂量依赖性降低急性内脏痛模型大鼠的腹壁撤退反射评分和腹外斜肌放电幅值(P〈0.05)。结论:ZD7288可抑制急性内脏痛大鼠的痛觉敏化,而背根神经节和脊髓的HCN2通道可能在其发病中起作用。 相似文献
7.
丹参治疗妊娠期高粘血症的疗效探讨 总被引:1,自引:0,他引:1
[目的]探索丹参对改善妊娠期高粘血症的作用。[方法]150例高粘血症孕妇随机分为三组,每组50例。观察组(A组)予丹参及扩容治疗,B组以不加丹参行扩容治疗及对照组(C组)不予治疗,比较三组治疗前后血液流变学及血管内皮素-1(ET-1)的变化。[结果]A组红细胞压积、血浆粘度、高及低切变率下的全血粘度均有降低(P〈0.05或P〈0.01);B组低切变率下的全血粘度、ET-1变化差异无显著性(P〉0.05);C组上述各指标差异无显著性(P〉0.05)。A组新生儿体重增加,羊水过少及胎儿生长受限(FGR)的发生率降低(P〈0.05)。[结论]妊娠期高粘血症的治疗,关键在于降低ET-1的释放,改善低切变率下的全血粘度,丹参能有效地降低孕妇的血粘度,改善围产儿的预后。 相似文献
8.
目的:观察自拟真人养脏汤治疗脾肾阳虚型溃疡性结肠炎的临床效果及不良反应,并与美沙拉嗪进行疗效比较。方法:将确诊的87例脾肾阳虚型溃疡性结肠炎患者随机分为治疗组43例与对照组44例,治疗组以自拟真人养脏汤加减治疗,对照组用美沙拉嗪治疗,疗程均为6周,比较两组患者的临床疗效及复发率。结果:治疗后两组患者在腹泻、黏液脓血便、腹痛、形寒肢冷、里急后重等症状以及综合疗效方面比较,治疗组均优于对照组,差异有统计学意义(P0.01或P0.05)。3个月内治疗组复发率(27.03%)与对照组(35.48%)的差异无统计学意义。结论:自拟真人养脏汤在治疗脾肾阳虚型溃疡性结肠炎方面疗效确切且安全,与美沙拉嗪治疗比较,在改善患者腹泻、黏液脓血便、腹痛、形寒肢冷、里急后重等症状更有优势,在防止复发方面差异不明显。 相似文献
9.
目的 探讨ZD1839对胰腺癌细胞的生长抑制作用机理.方法 应用MTT方法检测ZD1839对胰腺癌细胞的生长抑制作用、应用不同的生长因子刺激胰腺癌细胞的生长刺激,并检测ZD1839对不同生长因子作用的影响.应用western blot检测不同生长因子对EGF酪氨酸激酶受体的磷酸化作用,以及ZD1839对EGFR受体磷酸化的影响,并检测ZD1839对EGFR信号的下游MAPK磷酸化的影响.结果 ZD1839呈剂量依赖性抑制胰腺癌细胞的生长,ZD1839阻断EGF对胰腺癌细胞的生长刺激作用,但不阻断对IGF-1的作用.ZD1839抑制了基础的与EGF诱导的EGF受体磷酸化水平与MAPK的磷酸化水平.结论 结果表明,EGF对胰腺癌细胞有生长刺激作用,ZD1839对胰腺癌细胞的生长抑制作用是通过对抑制EGF受体磷酸化而特异性起作用的. 相似文献
10.
吉非替尼对肺癌细胞生长的抑制作用 总被引:1,自引:1,他引:1
目的探讨靶向治疗药物吉非替尼(ZD1839)对肺癌细胞生长的抑制作用。方法应用细胞培养和MTT等方法研究了ZD1839对13株人肺癌细胞生长的抑制作用。结果在13株肺癌细胞中,有一株肺癌细胞PC-9对ZD1839高度敏感,一株肺癌细胞A549中度敏感,有效率15.38%。其余11株肺癌细胞对ZD1839不敏感。结论吉非替尼是一种新型有效的肺癌分子靶向治疗药物。 相似文献