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1.
F. C. Howarth Allan J. Levi Jules C. Hancox 《Pflügers Archiv : European journal of physiology》1996,431(5):713-722
The delayed rectifier potassium current (I
K) is known to be important in action potential repolarisation and may contribute to the diastolic pacemaker depolarisation
in pacemaker cells from the heart. In this study, using whole-cell patch clamp, we investigated the characteristics of I
K in morphologically normal cells from the atrioventricular node (AVN) and ventricle of the rabbit heart. Cells were held at
−40 mV and 5 μM external nifedipine was used to block L-type calcium current (I
Ca,L). Significant I
K was observed with pulses to potentials more positive than −30 mV. The steady-state activation curve in both cell types showed
maximal activation at between + 10 and + 20 mV. Half-maximal activation of I
K occurred at −4.9 and −4.1 mV with slope factors of 8.3 and 12.4 mV in ventricular and AVN cells, respectively. Using pulses
of increasing duration, significant I
K tails after repolarisation from + 40 mV were observed with pulses of 20 ms and increased with pulses up to 100–120 ms in
both cell types. Pulses of longer duration did not activate further I
K and this suggested that only the rapid component of I
K, called I
Kr, was present in either cell type. Moreover, I
K tails after pulses to all potentials were blocked completely by E-4031, a selective blocker of I
Kr. The reversal potential of I
K varied with the concentration of external K. Superfusion of AVN cells with medium containing 4, 15 and 40 mM [K+]o resulted in reversal potentials of −81, −56 and −32 mV, respectively, which are close to values predicted if the I
K channel were highly selective for K. The time constants for deactivation of I
K in ventricle and AVN on return to −40 mV after a 500-ms activating pulse to + 60 mV were 480 ms and 230 ms, respectively.
The faster deactivation of I
K in AVN cells was a distinguishing feature and suggests that there may be differences in the I
Kr channel protein between ventricular and AVN cells.
Received: 24 July 1995 /Received after revision: 20 October 1995 /Accepted: 23 October 1995 相似文献
2.
Two new alleles, HLA-A*0108 and B*4031, were identified in north-western European Caucasoid subjects. A*0108 differed from A*010101 by a single substitution (C to T) at position 216 in exon 3, resulting in an amino acid difference of Arg to Trp at position 163. It was present on a haplotype with B*1501/60/70/71; Cw*0303; DRB1*1301; DRB3*0202; DQA1*0103; DQB1*0603 and its product reacted as a normal HLA-A1 specificity. B*4031 differed from B*4001 by two nucleotides in exon 3 (positions 20 (G to C) and 69 (A to G)) resulting in two amino acid differences (Arg to Ser at position 97 and Asn to Asp at position 114). It was found on a haplotype with HLA-A*03; Cw*0304; DRB1*0404/32; DRB4*0101/3/5; DQA1*03; DQB1*0302 and has the HLA-B60 specificity. Both alleles have frequencies of < 0.0002 in the largely north-western European Caucasoid blood donor population resident in Wales. 相似文献
3.
目的探讨环氧化物酶-2(cyclooxygenase type 2,COX-2)及Ⅰ型前列腺素合成酶(membrane associated prostaglandin E-1,mPGES-1)在人颈动脉粥样硬化斑块中的表达变化及作用机制。方法收集24例人颈动脉粥样硬化斑块标本和10例肠系膜动脉标本做对照组,应用免疫组织化学及逆转录PCR方法测定COX-2及mPGES-1mRNA表达水平,Western印记方法检测COX-2及mPGES-1的蛋白表达水平。比较不同程度动脉粥样硬化组织间COX-2、mPGES-1 mRNA表达水平及蛋白表达水平。结果颈动脉粥样硬化斑块组的免疫组织化学染色检测COX-2和mPGES-1呈阳性表达,斑块组COX-2 mRNA和mPGES-1 mRNA表达与对照组相比上调,差异有统计学意义(P<0.05);COX-2及mPGES-1 mRNA上调水平相关(P<0.05);颈动脉粥样硬化斑块的COX-2蛋白表达上调水平与对照组相比差异有统计学意义(P<0.05);颈动脉粥样硬化斑块COX-2、mPGES-1 mRNA及蛋白表达水平与病理损害程度有关,差异有统计学意义(P<0.05)。结论COX-2及mPGES-1基因表达水平上调可能是进展性动脉粥样硬化损害的关键因素。 相似文献
4.
Influence of antibody and complement components on phagocytosis and chemiluminescence of macrophages
Macrophages are known to release reactive oxygen species (O2?, 1O2, H2O2, OH·) in response to various membrane stimuliHowever, our studies show that phagocytic stimulation of macrophages is not necessarily accompanied by a stimulation of the oxidative burstWhereas IgG-opsonized erythrocytes were capable to induce phagocytosis and a chemiluminescence response, both being dependent on the number of IgG bound per erythrocyte, C3b-bearing erythrocytes were well ingested but failed to induce any chemiluminescence reactionFurthermore, stimulation of macrophages, via the Fc-receptors, seems to alter their functional state in regard to the activation of a receptor, which enables them to recognize membrane lesions on the target erythrocyteThe presence of IgG and membrane lesions, e.gthe C5b-9-complex of complement, induced a marked increase in chemiluminescence compared with stimulation by IgG-bearing particles aloneThe augmented response of macrophages was at least in part due to an additional release of H2O2, which was not liberated in response to IgG-bearing erythrocytesThis «Alesion recognizing receptor» in the macrophage membrane could not be activated by stimulation of C3b-receptors, indicating its functional linkage to the Fc-receptors. 相似文献
5.
T. Kawasaki K. Uezono I. Abe S. Nakamuta M. Ueno N. Kawazoe T. Omae 《European journal of clinical pharmacology》1981,20(6):399-405
Summary To determine whether E-643, a new -blocking agent, would reduce the blood pressure, regardless of the posture, a 1 mg dose was given 3 times daily for 7 consecutive days, to 8 male and 7 female inpatients, aged 37–73 years, with essential hypertension. Blood pressure and pulse rate were measured daily in the supine, sitting and standing positions. Before and after the treatment with E-643, plasma levels of noradrenaline, adrenaline, dopamine--hydroxylase, renin and aldosterone were determined, samples being obtained with the subjects recumbent and after standing upright for 60 min. A significant reduction in the systolic and diastolic blood pressures was evident in the supine (172±31/100±12 151±28/89±14 mmHg), sitting (158±22/101±11 138±28/89±15 mmHg) and standing (153±32/103±21 129±31/89±20 mmHg) positions. The reduction in blood pressure remained unchanged throughout the period of administration of E-643. Pulse rate was not affected when the subjects were supine (67±10 69±10 beats/min), but was increased in the sitting (68±10 73±9 beats/min) and standing (73±10 81±11 beats/min) positions. The increased pulse rate tended to decline during continued administration of E-643. Treatment with E-643 produced no significant change in plasma levels of adrenaline, noradrenaline, dopamine--hydroxylase, renin and aldosterone. The antihypertensive effect of treatment was more prominent in the patients with higher levels of plasma catecholamines and dopamine--hydroxylase, and was less prominent in those with higher plasma renin and aldosterone. Two patients had temporary bouts of dizziness and visual disturbances, but there were no subjective complaints during treatment. 相似文献
6.
目的 研究氯沙坦及其代谢产物2-丁基-4-氯-1-[[2’-(1H-四唑-5-基)[1,1‘-联苯基]-4-基]甲基]-lH一咪唑-5-羧酸(E-3174)在中国汉族健康受试者体内的药动学。方法 10名健康受试者,男女各半,口服氯沙坦钾片50 mg,定时采血,用HPLC荧光法测定氯沙坦及其代谢物E-3174血药浓度,DAS2.0软件程序进行数据处理并采用SPSS13.0软件进行统计学分析。结果 氯沙坦和E-3174的主要药动学参数如下:ρmax分别为( 351±167),( 241±60) μg·L-1; tmax分别为(1.35±1.06),(3.60±1.68) h;t1/2分别为(0.82±0.40),(4.66±1.10) h;AUC0-24分别为(498±172),(1 853±194) μg ·h·L-1;AUC0-∞分别为(523±184),(1 960±182) μg ·h·L-1。结论 氯沙坦及其代谢物E-3174的药动学特征和参数在个体间存在较大差异,临床治疗中应实行个体化给药方案。 相似文献
7.
目的:对金粟兰属植物银线草Chloranthus japonicus Sieb.全草的化学成分进行研究,以探究其药理活性物质基础。方法:采用硅胶、凝胶Sephadex LH-20、半自动制备液相等色谱方法对银线草的乙酸乙酯部位进行分离纯化,通过1D-NMR、紫外(UV)光谱、质谱(MS)技术对化合物的结构进行鉴定。结果:从银线草75%乙醇提取物的乙酸乙酯部位共分离得到9个化合物,分别鉴定为金合欢素(1)、千层纸素A(2)、7 E-3,4-二氧甲基苯并[2-苯基-胸苷](3)、落叶松脂素(4)、9α-羟基紫菀内酯(5)、银线草醇B(6)、金粟兰素C(7)、白术内酯Ⅲ(8)、白术内酯Ⅱ(9)。结论:化合物14为首次在金粟兰属中分离得到。 相似文献
8.
目的:研究进食对健康受试者单剂量口服氯沙坦钾片药动学的影响。方法:10名健康受试者随机分为2组,每组5人。试验开始前一晚禁食10h,晨起后,一组空腹口服氯沙坦钾片50mg,另一组在进食后口服氯沙坦钾片50mg。经1周清洗期后,两组交叉试验。采用高效液相色谱串联质谱电喷雾(HPLC-MS/MS)法测定人血浆中氯沙坦及其代谢产物E-3174的浓度,采用DAS2.1.1软件计算药动学参数并比较进食或空腹对药动学的影响。结果:空腹和进食后服用氯沙坦钾片,血浆原型药物tmax分别为(1.33±0.60)、(2.20±1.09)h,cmax分别为(268.51±192.39)、(138.11±32.84)μg.L-1,AUC0~12分别为(442.83±171.05)、(401.54±98.43)μg.h.L-1,t1/2z分别为(1.59±0.22)、(1.74±0.59)h,MRT0~12分别为(2.74±0.69)、(3.57±0.91)h;代谢产物E-3174的cmax分别为(890.6±239.13)、(904.9±415.88)μg.L-1,tmax分别为(4.60±1.58)、(5.00±1.41)h,AUC0~36分别为(6407.54±1243.00)、(6417.02±2472.92)μg.h.L-1,t1/2z分别为(5.25±3.46)、(4.64±1.46)h,MRT0~36分别为(8.34±1.52)、(8.95±1.24)h。上述药动学参数差异经t检验无统计学意义(P>0.05)。结论:空腹和进食后服用氯沙坦钾片,原型药物和起主要降压作用的代谢产物E-3174的各药动学参数无显著性差异,可认为进食对本药在健康人体内的代谢无影响。 相似文献
9.
10.