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101.
目的:观察心肌梗死后心力衰竭大鼠血管内皮功能和心功能的变化与血管紧张素转换酶抑制剂培哚普利的干预关系。方法:实验于2004-12/2006-03于中山大学附属第二医院医学实验中心完成。实验动物:成年雄性SD大鼠75只,体质量250~300g。实验分组:取60只大鼠结扎冠状动脉左前降支建立心肌梗死大鼠模型,另取15只为假手术组做对照。实验方法:术后1周行超声心动图检查,以centerline方法判断心肌梗死面积。术后第2周,心肌梗死大鼠中30只给予培哚普利灌胃,另30只为对照组给予盐水灌胃。评估标准:10周后测定左室血流动力学参数,循环血液中一氧化氮,内皮素-1和C-反应蛋白的水平,并观察离体胸主动脉环对内皮依赖性扩血管物质乙酰胆碱的舒张反应。结果:75只大鼠进入结果分析:①血浆内皮素-1和血清一氧化氮、C-反应蛋白含量的变化:与假手术组相比,心肌梗死盐水组血浆内皮素-1水平上升,血清一氧化氮含量下降,血清C-反应蛋白水平升高(P均<0.05);与心肌梗死盐水组相比,培哚普利治疗组血浆内皮素-1水平下降,血清一氧化氮含量上升,血清C-反应蛋白水平下降(P均<0.05)。②各组大鼠胸主动脉环对乙酰胆碱的反应性测定:心肌梗死盐水组胸主动脉环对乙酰胆碱介导的最大舒张反应显著小于假手术组和培哚普利治疗组(39.5±6.38,79.4±7.59,67.9±6.92,P均<0.05);与假手术组相比,心肌梗死盐水组胸主动脉环对各个浓度的乙酰胆碱介导的舒张反应显著减弱(P均<0.05);与心肌梗死盐水组相比,培哚普利治疗组显著改善各个浓度乙酰胆碱介导的舒张反应(P均<0.05)。③各组大鼠血流动力学指标改变:与假手术组相比,心肌梗死盐水组大鼠出现明显的心力衰竭,表现为左室内收缩压降低,左室舒张末期压升高,室内压最大上升/下降速率降低(P均<0.05);与心肌梗死盐水组相比培哚普利治疗组大鼠的心功能显著改善(P均<0.05)。④各组大鼠存活率:10周后培哚普利治疗组存活率显著高于心肌梗死盐水组(67%,43%,P<0.05)。结论:心肌梗死大鼠血管内皮功能和心功能在长期应用培哚普利治疗后得到改善,其机制可能与抑制炎症反应有关。 相似文献
102.
JF Thiercelin 《Fundamental & clinical pharmacology》1990,4(S2):69s-76s
Summary— The aim of phase I studies per se is to explore the tolerance of new compounds which have demonstrated a certain level of activity in animals at sufficiently low non-toxic doses. In most cases, these studies are conducted in 2 steps in a limited number of healthy male volunteers: a single rising dose study followed by a repeated dose study in which the pharmacokinetic features of the drug are explored. In such a context, it would be quite presumptuous to ascertain the therapeutic efficacy of a drug from those initial human studies. At best, these trials can provide pharmacological and/or biological indications which are related to some degree to the expected efficacy of the drug: hypnotics, anticancer drugs, antibiotics, platelet antiaggregants, beta-blockers, etc. In these examples it is recommended to design controlled study protocols so as to better investigate these potentially interesting signs of activity. In the majority of cases, however (psychoactive drugs, analgesic, anti-inflammatory drugs, gastro-intestinal compounds), phase I studies will unfortunately not provide much information regarding the expected therapeutic activity. 相似文献
103.
Oral cyclophosphamide versus chlorambucil in the treatment of patients with membranous nephropathy and renal insufficiency 总被引:4,自引:1,他引:4
Branten AJ; Reichert LJ; Koene RA; Wetzels JF 《QJM : monthly journal of the Association of Physicians》1998,91(5):359-366
We treated patients with idiopathic membranous nephropathy (iMGN) and renal
insufficiency, using: (i) (n = 15) monthly cycles of steroids (1 g
methyl-prednisolone i.v. on three consecutive days, followed by oral
prednisone 0.5 mg/kg/day months 1, 3 and 5) and chlorambucil (0.15
mg/kg/day months 2, 4 and 6); or (ii) (n = 17) oral cyclophosphamide
(1.5-2.0 mg/kg/day for 1 year) and steroids in a comparable dose. The
groups were comparable in age, renal function and levels of proteinuria.
During the 6 months preceding treatment, serum creatinine levels increased
from 148 +/- 50 to 219 +/- 73 mumol/l in the chlorambucil group and from
164 +/- 86 to 274 +/- 126 mumol/l in the cyclophosphamide group. Median
(range) follow-ups were: chlorambucil 38 months (8-71); cyclophosphamide 26
months (5-68) (NS). Renal function improved in both groups, but the
improvement was short-lived in the chlorambucil group; 12 months after
starting treatment, mean serum creatinine was 6.3 mumol/l lower in the
chlorambucil group and 121 mumol/l lower in the cyclophosphamide group (p
< 0.01). Four chlorambucil-treated patients developed ESRD, and five
needed a second course of therapy, whereas only one
cyclophosphamide-treated patient developed ESRD (p < 0.05). Remissions
of proteinuria occurred more frequently after cyclophosphamide treatment
(15/17 vs. 5/15; p < 0.01). Side-effects necessitated interruption of
treatment in six patients on cyclophosphamide and in 11 on chlorambucil (p
< 0.05). In our patients, oral cyclophosphamide was better tolerated
than oral chlorambucil. The suggested greater efficacy of the oral
cyclophosphamide regimen needs to be ascertained by longer follow-up.
相似文献
104.
A Bellou JD de Korwin F Boman-Ferran JF Cuny M Kessler 《La Revue de médecine interne / fondée ... par la Société nationale francaise de médecine interne》1995,16(12)
Malignant lymphoma particularly of T phenotype can be associated with specific or non specific cutaneous lesions. These cutaneous manifestations can occur at the onset of the disease being sometimes the revealing sign or they can appear during the course of the lymphoreticular malignancies. Glomerulonephritis was also described in lymphoma. Ki- positive large cell lymphoma was recently identified. A new case is reported with lymphadenopathy and intestinal localisation revealed by cutaneous and mucosal ulcerations principally in the mouth and a focal segmental glomerulonephritis with endo- and extracapillary proliferation. The absence of lymphoma in cutaneous and renal lesions and the clinical presentation support the hypothesis of paraneoplastic manifestations, may be related to a vasculitis. 相似文献
105.
106.
Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications 总被引:1,自引:0,他引:1
Platelets have a central role in the development of arterial thrombosis and subsequent cardiovascular events. An appreciation of this complex process has made antiplatelet therapy the cornerstone of cardiovascular disease management. However, numerous patients will experience a recurrent atherothrombotic vascular event despite adequate antiplatelet therapy. Individual differences in the rate of platelet activation and reactivity markedly influence normal hemostasis and the pathological outcome of thrombosis. Such an individual variability is largely determined by environmental and genetic factors. These are known to either hamper platelets' response to agonists, and thereby mimic the pharmacological modulation of platelet function or mask therapy effect and sensitize platelets. In this article, we reviewed the antiplatelet mechanisms of aspirin and clopidogrel and the possible role of different polymorphisms, which may affect the efficacy of antiplatelet therapy. Heterogeneity in the way patients respond to aspirin and clopidogrel may in part reflect variation in cyclooxygenase (COX)-1, COX-2, glycoprotein (GP) Ib alpha, GP Ia/IIa, GP IIb/IIIa, UGT1A6*2, P2Y1 , P2Y12 , CYP2C9, CYP3A4 and CYP3A5 genotypes. 相似文献
107.
GM Repetto ML Guzmán A Puga JF Calderón CP Astete M Aracena M Arriaza T Aravena P Sanz 《Clinical genetics》2009,76(5):465-470
Patients with chromosome 22q11 deletion syndrome exhibit significant phenotypic variability. Epidemiologic data suggest a higher incidence in Hispanics, but limited clinical information is available from Latin-American patients. We describe the clinical features of Chilean patients with 22q11 deletion syndrome and compare their findings with those reported in large European, Japanese and US series. Data were obtained from 208 patients from five medical centers. Mean age at diagnosis was 5.2 years, with a median of 2.3 years. Congenital heart defects were present in 59.6%, lower than other large series that averaged 75.8%. Palate abnormalities were present in 79%, higher than previous reports averaging 56%. Patients with congenital heart disease were diagnosed earlier (median 0.3 years of age) than those without heart defects (median 5.6 years) and had greater mortality attributable to the syndrome (9.8% vs 2.4%, respectively). The differences in frequencies of major anomalies may be due to growing awareness of more subtle manifestations of the syndrome, differences in clinical ascertainment or the presence of modifier factors. These observations provide additional data useful for patient counseling and for the proposal of health care guidelines. 相似文献
108.
109.
Diabetes, oxidative stress, and platelet activation 总被引:1,自引:0,他引:1
110.
The nuclear concentration of kin17, a mouse protein that binds to curved DNA, increases during cell proliferation and after UV irradiation 总被引:2,自引:1,他引:1
Kannouche P; Pinon-Lataillade G; Tissier A; Chevalier-Lagente O; Sarasin A; Mezzina M; Angulo JF 《Carcinogenesis》1998,19(5):781-789
UV-irradiation induces, in mammalian cells, the expression of a set of
genes known as the 'UV-response', which may be reminiscent of the bacterial
response, called SOS system. The multifunctional protein RecA controls the
expression of the SOS genes. We report the expression profile of a mouse
gene conserved among mammals, called Kin17, that codes a DNA-binding
protein of undetermined biochemical activity and which shares epitopes with
the bacterial RecA protein. We demonstrate that the level of Kin17 RNA was
5-fold higher in mid-S phase of serum- stimulated BALB/c 3T3 fibroblasts
than in quiescent cells. Cells in S- phase displayed a high level of kin17
protein with a marked nuclear localisation. The maximal level of Kin17 RNA
was observed 18 h after serum stimulation, indicating that Kin17 gene is a
new member of the late growth-related genes. The accumulation of kin17
protein during cell proliferation follows the increase in Kin17 RNA and
correlates with DNA synthesis, which suggests a possible role of kin17
protein in a transaction related to DNA-replication. In quiescent
fibroblasts, a 3- fold increase in Kin17 RNA was seen 13 h after UV
irradiation. In parallel, kin17 protein accumulated in the nucleus, which
suggests that it might be required after the stress produced by UV
irradiation.
相似文献