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排序方式: 共有56条查询结果,搜索用时 31 毫秒
1.
Shohei Takeda Yutaka Inada Yoshiki Ozawa Narue Nakamizo Teruaki Tomaru 《Journal of anesthesia》1995,9(2):176-181
The cardiovascular responses to an infusion of KRN2391, a potassium channel opener, was studied in halothane-anesthetized
dogs. Intravenous administration of KRN2391 at 1.0 and 5.0 μg·kg−1·min−1 for 60 min produced dose-dependent decreases in mean arterial pressure (MAP) and systemic vascular resistance (SVR) associated
with dose-dependent increases in the cardiac index (CI) and stroke volume index (SVI) but was not accompanied by an increase
in heart rate (HR). The maximum decrease in MAP during the infusion of KRN2391 at 1.0 and 5.0 μg·kg−1·min−1 was −13±7% (P<0.01) and −37±10% (P<0.01), respectively. The maximum reduction in SVR after 1.0 and 5.0 μg·kg−1·min−1 was −20±11% (P<0.01) and −60±16% (P<0.01), respectively. A KRN2391 infusion of 1.0 and 5.0 μg·kg−1·min−1 increased Cl a maximum of 11±13% (P<0.05) and 65±33% (P<0.01), respectively. KRN2391 1.0 μg·kg−1·min−1 showed a tendency to increase SVI but this change was not significant, KRN2391 5.0 μg·kg−1·min−1, however, produced a significant increase in SVI. The present results demonstrate that the decrease in MAP and the increases
in CI and SVI caused by KRN2391 are due to a reduction in the afterload. Therefore, we conclude that these cardiovascular
profiles of KRN2391 may be benificial in perioperative uses including the control of systemic blood pressure and the treatment
of hypertension during halothane anesthesia in clinical practice. 相似文献
2.
目的:探讨ATP敏感性钾通道(KATP通道)开放剂KRN2391(KRN)对离体大鼠心功能及心肌梗死范围的影响。方法:用Langendorff装置,观察不同浓度KRN对冠脉灌流量及左心室压力的影响。应用离体大鼠双冠脉分别灌注芊45min缺血及2h再灌注,观察药物对心肌梗死面积的影响。结果:KRN在达到1umol/L浓度后冠脉灌流量明显增加,达20umol/L时左室收缩压明显下降,用1umol/LK 相似文献
3.
Frances M. Sobierajski Graeme M. Purdy Charlotte W. Usselman Rachel J. Skow Marina A. James Radha S. Chari Rshmi Khurana Michael K. Stickland Sandra T. Davidge Maureen Devolin Craig D. Steinback Margie H. Davenport 《The Canadian journal of cardiology》2018,34(4):485-491
Background
Cardiovagal baroreflex gain (cBRG) reflects an individual's ability to buffer swings in blood pressure. It is not well understood how this mechanism is influenced by physical activity in pregnancy. Because pregnant women tend to engage in low levels of moderate-to-vigorous physical activity (MVPA) and high levels of sedentary behaviour, we sought to determine the influence of MVPA and sedentary behaviour on cBRG and mean arterial pressure (MAP) in pregnancy.Methods
Fifty-eight third trimester (31.9 ± 3.0 weeks) normotensive pregnant women (31.2 ± 2.8 years) were tested. Heart rate (electrocardiogram) and blood pressure (systolic blood pressure and MAP; finger photoplethysmography) were collected on a beat-by-beat basis, and averaged over 3 minutes of rest. Spontaneous cBRG was calculated as the slope of the relationship between fluctuations in systolic blood pressure and heart rate. Objective measures of MVPA and sedentary behaviour were collected over a 7-day period using an ActiGraph accelerometer (model wGTX3-BT; ActiGraph LLC, Pensacola, FL).Results
Participants spent 67.5 ± 7.9% of waking hours engaged in sedentary behaviour, and performed 68.6 ± 91.9 minutes of MVPA per week. Sedentary behaviour was not related to cBRG (r = ?0.035; P = 0.793) or MAP (r = ?0.033; P = 0.803). However, MVPA was positively associated with cBRG (r = 0.315; P = 0.016), but not MAP (r = ?0.115; P = 0.389). The association between MVPA and cBRG remained significant after controlling for age, pre-pregnancy body mass index, gestational age, and wear time (r = 0.338; P = 0.013), indicating that women who engaged in greater amounts of MVPA showed increased cBRG.Conclusions
Our data suggest that increased MVPA, but not necessarily reduced sedentary behaviour, might be beneficial for reflex control of blood pressure during pregnancy. 相似文献4.
M. Kamishohara Hiroyuki Kawai Teruyuki Sakai Takeshi Uchida Takashi Tsuruo Noboru Otake 《Cancer chemotherapy and pharmacology》1996,38(6):495-498
The inhibitory effect of KRN5500, a spicamycin derivative, on the growth of hepatic metastasis of the tissue polypeptide
antigen (TPA)-producing human colon cancer COL-1 was examined in severe combined immunodeficient (SCID) mice. Prior to this
chemotherapeutic study, we confirmed the high correlation coefficient (r=0.86, P<0.01) between plasma TPA levels in athymic nude mice bearing COL-1 and tumor volume. In the chemotherapy of experimental
hepatic metastasis induced by intrasplenic injection of COL-1 cells, KRN5500 at 12 mg/kg per day was administered i.v. three
times at 4-day intervals. From the start of chemotherapy (day 1), plasma TPA levels in the mice were significantly decreased
from 8332 U/l to a minimum of 494 U/l on day 16 and were within the range for intact SCID mice (409–634 U/l). The mean tumor
weight was 4.87 g in the liver of untreated mice on day 19 and 0.74 g, in the liver of KRN5500-treated mice, a significant difference, representing a tumor growth inhibition rate of 85%. These
results suggest the usefulness of TPA as a tumor marker in an experimental xenograft model. The chemotherapeutic efficacy
of KRN5500 against experimental hepatic metastasis indicates that it may be a useful drug for the treatment of patients with
hepatic metastases of colon cancer.
Received: 26 June 1995/accepted: 6 December 1995 相似文献
5.
KRN2391: dual action on rat pulmonary artery and no loss of potency in pulmonary hypertension 总被引:1,自引:0,他引:1
Wanstall JC Gambino A Thomas BJ 《Clinical and experimental pharmacology & physiology》2000,27(4):288-294
1. The pulmonary vasorelaxant properties of KRN2391 (N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide) were examined in isolated ring preparations of main (MPA) and intralobar (IPA) pulmonary artery from control and pulmonary hypertensive rats (exposure to hypoxia, 10% oxygen, for 1 week). 2. On both MPA and IPA, pulmonary vasorelaxant responses were inhibited by methylene blue (10 micromol/L) or glibenclamide (1 or 10 micromol/L). Thus, KRN2391 has the properties of both a nitric oxide (NO) donor and a K(ATP) channel opener on rat pulmonary arteries. 3. KRN2391 was more potent and gave a greater maximum relaxation on MPA (-log EC(50) 6.47; maximum 92% reversal of induced contraction) than on IPA (-log EC(50) 6.09; maximum 58% reversal of induced contraction). Comparable differences between MPA and IPA were seen for SIN-1 (NO donor) and levcromakalim (K(ATP) channel opener). 4. KRN2391 was equipotent in MPA from control and pulmonary hypertensive rats but, when glibenclamide (10 micromol/L) was present, KRN2391 was six-fold less potent in preparations from pulmonary hypertensive than control rats. An eight-fold reduction in potency was seen for SIN-1 (no glibenclamide) in arteries from pulmonary hypertensive rats, confirming previous findings with other NO donors. 5. It is concluded that the dual mechanism of action of KRN2391 accounts for the finding that this drug is equally potent in pulmonary arteries from pulmonary hypertensive and control rats. In the context of pulmonary hypertension, this property of the drug could give it an advantage over drugs that act solely as NO donors because these decline in potency, at least in animal models of this disease. 相似文献
6.
Kanzawa F Nishio K Fukuoka K Sunami T Saijo N 《Cancer chemotherapy and pharmacology》1999,43(5):353-363
Purpose: KRN5500 is a new derivative of spicamycin produced by Streptomyces alanosinicus and is known to have a wide range of antitumor activities against human cancer cell lines. Because of its unique structure,
this compound seems to have a different mode of action from other antitumor drugs and nonoverlapping toxicities. Therefore,
KRN5500 is expected to be a suitable candidate for combination chemotherapy. Methods: We investigated the effects of combinations of KRN5500 and other anticancer drugs on the growth of a human non-small-cell
lung cancer cell line, PC14, using a revised three-dimensional model. Results: Synergism was observed when KRN5500 and cisplatin were combined at concentrations in the ranges 0.005 to 0.25 μg/ml and
0.025 to 0.25 μg/ml, respectively. In combination with carboplatin, an analog of cisplatin, and etoposide, a marked synergistic
interaction was also found. Conclusion: These results suggest the usefulness of combinations of KRN5500 with cisplatin, carboplatin or etoposide for chemotherapy
for non-small-cell lung cancer.
Received: 27 April 1998 / Accepted: 15 September 1998 相似文献
7.
Reduction of the Side Effects of an Antitumor Agent, KRN5500, by Incorporation of the Drug into Polymeric Micelles 总被引:1,自引:0,他引:1
Yasuhiro Matsumura Masayuki Yokoyama Kazunori Kataoka Teruo Okano Yasuhisa Sakurai Takanori Kawaguchi Tadao Kakizoe 《Cancer science》1999,90(1):122-128
For intravenous (i.v.) injection of a water-insoluble antitumor drug, KRN5500, we have successfully incorporated KRN5500 into polymeric micelles. In the present study, in vitro and in vivo antitumor activity against several human tumor cell lines and toxicity in mice of polymeric micelles incorporating KRN5500 (KRN/m) were evaluated in comparison with those of the prototype KRN5500. KRN/m was found to express similar antitumor activity to KRN5500 in the in vitro and in vivo systems. However, the vascular damage and liver focal necrosis observed with KRN5500 i.v. injection were not seen when KRN/m was administered i.v. Therefore, we expect that KRN/m will be superior to KRN5500 for clinical use and that the methodology of polymeric micelle drug carrier systems can be applied to other water-insoluble drugs. 相似文献
8.
Purpose. The hemodynamic profiles of KRN2391-induced hypotension have been reported to be a hyperdynamic state. However, the endocrine
effects of KRN2391-induced hypotension remain to be elucidated. We investigated the endocrine and metabolic effects of KRN2391-induced
hypotension on the plasma concentrations of catecholamines, aldosterone, cortisol, glucose, and lactic acid and on plasma
renin activity.
Methods. Eight dogs were anesthetized with 087% halothane in oxygen. After a baseline period, mean arterial pressure (MAP) was lowered
to 60 mmHg for 60min by the infusion of KRN2391.
Results. KRN2391-induced hypotension resulted in a 50% decrease (P<0.01) in MAP due to a 80% reduction (P<0.01) in systemic vascular resistance associated with a 224% increase (P<0.01) in cardiac index. Plasma norepinephrine concentrations increased (P<0.01) after 60 min of hypotension. Plasma epinephrine concentrations and plasma renin activity both increased (P<0.05) during the hypotensive period. Plasma aldosterone concentrations remained unchanged during the hypotensive period,
but then increased (P<0.05) after termination of KRN2391. Plasma cortisol concentrations remained unchanged throughout the observation period.
Plasma glucose concentrations increased (P<0.01) during the hypotensive period. Plasma lactic acid concentrations increased (P<0.01) throughout the observation period.
Conclusion. KRN2391-induced hypotension activates the sympathetic nervous system and consequently may modulate the renin-angiotensin-aldosterone
axis and carbohydrate metabolism. 相似文献
9.
10.
Giles FJ 《Leukemia research》2006,30(12):1469-1470
Aberrant FLT3 function in leukemia blasts is associated with a poor prognosis. A number of FLT3 modulators are in development. FLT3 mutations may synergistize with other molecular abnormalities in myeloid transformation. Further insights into FLT3 biology are needed to optimally study the therapeutic role of FLT3 inhibitors. 相似文献