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41.
Nobuyuki Hamajima Atsuko Shibata Yuzuru Ikehara Nobuyuki Katsuda Sayomi Mori Hidemi Ito Keitaro Matsuo Kazuo Tajima Suketami Tominaga 《Gastric cancer》2002,5(4):0194-0200
Background: In our previous study, a marked association between
Helicobacter pylori
seropositivity and functional polymorphisms of the
secretor
and
Lewis
genes (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.14–0.70 for
se/se
genotype relative to
Se/Se
genotype; and OR, 10.3; 95% CI, 3.16–33.8 for high-risk group defined by the combination of
Se
and
Le
relative to low-risk group) had been observed for 239 non-cancer Japanese outpatients of the gastroenterology clinic (OGC)
undergoing gastroscopy at Aichi Cancer Center Hospital.
Methods: The present study was a confirmatory study to examine the association for 679 first-visit outpatients (FVO) of all clinics
at the same cancer hospital and for 465 health checkup examinees (HCE) in the same city.
Results:
The associations between
H. pylori
seropositivity and the
Se
and
Le
genotypes were nonsignificant or even in the opposite direction among the FVO (OR, 1.52; 95% CI, 1.00–2.32 for
se/se
genotype relative to
Se/Se
genotype; and OR, 0.77; 95% CI, 0.43–1.40 for the high-risk group defined similarly to the previous study), and among the
HCE (OR, 1.25; 95% CI, 0.75–2.07; and OR, 1.07; 95% CI, 0.50–2.26, respectively). The discrepancy between the previous and
present results was not explained by the difference in the distributions of age, sex, smoking, and
H. pylori
seroprevalence.
Conclusion: Even in the same ethnic group, different sources of subjects may demonstrate inconsistent findings due to an unidentified
effect modification. Inconsistent findings have rarely been reported by the same research group, but they are very important
to understand the whole picture of the association under study.
Received: May 9, 2002 / Accepted: July 2, 2002
Acknowledgments This work was supported in part by a Grant-in-Aid for the Second Term Comprehensive 10-Year Strategy for Cancer Control from
the Ministry of Health, Labour and Welfare of Japan. The authors are grateful to Ms. Naomi Takeuchi for genotyping.
Offprint requests to: N. Hamajima 相似文献
42.
Winker R Barth A Valic E Maier R Osterode W Pilger A Rüdiger HW 《International archives of occupational and environmental health》2005,78(3):171-177
Objectives: Idiopathic orthostatic intolerance (IOI) is a common disorder that is characterized by chronic orthostatic symptoms and substantial increases in heart rate and plasma norepinephrine concentrations that are disproportionately high while standing. Several features of the syndrome, including the tachycardia, tremulousness, and exaggerated norepinephrine have been considered potentially due to hypoactive or hyperactive states of adrenergic receptors of the sympathetic nervous system. The aim of this study was therefore to ascertain whether genotypes at eight polymorphic loci within five relevant adrenergic receptor genes (2A, 2B, 2C, 1 and 2) influence the risk for IOI. Methods: We studied 80 young men in military service (20 patients with IOI and 60 age-matched controls). All participants underwent a tilt table test including monitoring of blood pressure, heart rate and plasma catecholamines, in the supine position and during 30 min of standing. Genotyping at the eight loci (2ALys251, 2BDel301-303, 2CDel322-325, 1Gly49, 1Arg389, 2Arg16, 2Glu27, 2Ile164) was performed in all participants. Chi-square tests of independence were used to test for associations between IOI and genotype. In addition, an association of the polymorphisms with haemodynamic variables (heart rate, supine and upright blood pressure) was ascertained using one-way variance analysis. Results: For the 1Gly49 polymorphism we found a decrease in the risk of IOI among persons who were homozygous (odds ratio, 0.88; 95% confidence interval, 0.81–0.97). In addition, we found an association between 1Gly49 and decreased heart rate in the upright position, regardless of IOI diagnosis. There were no associations with the other studied polymorphisms and IOI. Conclusions: Our current results suggest that the 1Gly49 polymorphism is protective for IOI. This is likely one of several common genetic loci that may represent modifiers of IOI phenotypes. 相似文献
43.
Nagassaki S Metzger IF Souza-Costa DC Marroni AS Uzuelli JA Tanus-Santos JE 《Thrombosis research》2005,115(5):375-379
INTRODUCTION: Nitric oxide (NO) plays an important role in the regulation of the cardiovascular system. It is produced by endothelial nitric oxide synthase (eNOS), which exhibits genetic polymorphisms. Although the clinically relevant polymorphism T(+IhI-786)C reduces eNOS-promoter activity, it is not clear whether circulating nitrite/nitrate (NOx) are affected by this polymorphism. MATERIALS AND METHODS: We addressed this issue by studying a homogeneous group of 200 healthy subjects (males, Caucasians, nonsmokers, 18+IBM-56 years of age, and not taking any medication). Genotypes were determined by restriction fragment length polymorphism and circulating NOx were determined by chemiluminescence. RESULTS: We found nonsignificant effects of the T(+IhI-786)C polymorphism on circulating NOx (mean+ALE-S.D.=52.2+ALE-21.4, 49.0+ALE-17.8, and 45.9+ALE-16.8 +A7w-mol/L for genotypes +IBw-TT,+IB0 +IBw-TC,+IB0 and +IBw-CC,+IB0 respectively) and on total plasma cholesterol concentrations (both P>.05). No correlation was found between circulating NOx and total plasma cholesterol concentrations (P>.05). CONCLUSIONS: Our study provides strong evidence that the T(+IhI-786)C polymorphism does not affect plasma NOx concentrations, which are believed to reflect endogenous production of NO. Therefore, our results suggest that this polymorphism does not affect endogenous NO production. 相似文献
44.
Lindman AS Pedersen JI Arnesen H Hjerkinn EM Veierød MB Prydz H Seljeflot I 《Thrombosis research》2004,113(1):57-65
INTRODUCTION: Elevated levels of coagulation factor VII (FVII) have been associated with increased risk for myocardial infarction (MI). The R353Q polymorphism of the FVII gene has been shown to modify plasma levels of FVII, and has in some studies also been associated with reduced risk for MI. OBJECTIVES: To examine the R353Q polymorphism of the FVII gene and the relation to myocardial infarction (MI), cardiovascular disease (CVD), and diabetes, and furthermore, to elucidate the association between the polymorphism and plasma levels of FVII coagulant activity (FVIIc), FVII antigen (FVIIag), activated FVII (FVIIa), and serum choline-containing phospholipids (PC). METHODS: In 560 elderly men characterised as hypercholesterolemic in 1972, we examined the R353Q polymorphism by melting curve analysis after real-time PCR. In a subgroup of 205 individuals, FVIIc, FVIIag, FVIIa, and PC were analysed. RESULTS: There were no significant associations between genotype and the disease states, although we observed a lower number of MI cases among subjects with the Q allele, compared to the RR individuals (14% vs. 19%). FVIIag and FVIIc levels were lower in RQ compared to RR subjects, whereas for FVIIa the opposite was observed (p<0.001 for all). PC correlated positively with FVIIag (r=0.24, p<0.001), but negatively with FVIIa (r=-0.25, p<0.001). No genotype specific interactions were found for the association between FVII and PC. CONCLUSION: No significant associations between the R353Q polymorphism and MI, CVD, or diabetes were observed, although the polymorphism strongly influenced plasma levels of FVII. Serum PC correlated significantly with FVIIag and inversely with FVIIa, independently of genotype. 相似文献
45.
Neuhaus T Geisen G Bolt HM Janzen V Kraemer A Vetter H Ko Y 《Archives of toxicology》2004,78(7):390-396
Molecular epidemiological studies require high numbers of participants. The combination of an non-invasive access to human DNA with a rapid genotyping analysis, e.g. by use of LightCycler assisted real-time polymerase chain reaction (PCR), can be helpful in conducting such trials. The aim of our study was to define, for the first time, the use of LightCycler technology in analysis of non-invasively derived DNA. DNA extracted from blood, mouthwash and buccal cytobrush samples from 100 volunteers was analyzed for the genotypes of cytochrome P450 CYP1B1, and glutathione S-transferases GSTT1, GSTM1 and GSTP1. The median amounts of DNA isolated from blood, mouthwash and buccal cytobrush samples were 95, 11 and 8 µg, respectively. While genotyping for CYP1B1 codon 432 polymorphism and GSTP1 codon 105 polymorphism resulted in a complete correspondence for all three modes of sampling, the identification of individuals with null-genotype for GSTT1 or GSTM1 failed in some cases due to atypical courses of the corresponding melting curves, leading to high false-positive rates in the group of non-invasively derived samples. Thus, the results presented here call for caution in using LightCycler assisted real-time PCR in non-invasively collected samples, at least when appropriate control strategies are not implemented.T. Neuhaus and G. Geisen contributed equally to this work 相似文献
46.
Dennis L. Murphy Qian Li Sharon Engel Christine Wichems Anne Andrews Klaus-Peter Lesch George Uhl 《Brain research bulletin》2001,56(5):487-494
The serotonin transporter (5-HTT) is most well known as the site of action of the serotonin reuptake inhibitors, which were initially developed as antidepressants, but now are the most widely used agents in the treatment of many additional neuropsychiatric and related disorders. The discovery that the gene that expresses the 5-HTT possesses a functional promoter-region polymorphism, which is associated with temperament and personality traits such as anxiety and negative emotionality as well as some behaviors, led to many studies examining this polymorphism in individuals with different neuropsychiatric disorders. The subsequent development of mice with a targeted disruption of the 5-HTT in our laboratory has provided an experimental model to examine the many consequences of diminished (in +/-, heterozygote mice) or absent (in -/-, homozygote knockout mice) function of the 5-HTT. The 5-HTT-deficient mice were also crossed with other knockout mice, allowing the study of multiple neurobiologic dysfunctions. As multiple genes are probably involved in the expression of complex behaviors such as anxiety, as well as neuropsychiatric disorders, these more genetically complex mice may more closely model disorders with complex etiologies. Thus, the combination of these comparative human and mouse studies may extend the opportunities to examine genetic alterations from a novel "bottom-up" approach [gene knockout or partial gene knockout in a combinational gene x gene x (yet unknown) gene approach], which is complementary to the traditional "top-down" genetic approach based upon studies of individuals with diagnosed neuropsychiatric disorders and their family members. 相似文献
47.
目的探讨肾素血管紧张素系统(RAS)中的血管紧张素转换酶(angiotensin 1-converting enzyme,ACE)基因多态性与黑龙江地区人群非家族性房颤的发生关系。方法选取ACE基因I/D位点进行分析。采用病例-对照实验设计,研究对象共400例,均来自黑龙江省,包括非家族性房颤者200例和对照组200例。本研究采用聚合酶链反应(polymerase chain reaction,PCR)技术。结果ACEI/D位点与房颤发生显著相关,疾病组中的ACE-D等位频率显著高于对照组。结论RAS基因可能不仅是高血压病的候选基因,也有可能是非家族性房颤的候选基因。 相似文献
48.
目的探讨MMP-9基因启动子区的单核苷酸多态性与子宫内膜异位症遗传易感性的关系。方法采用蛋白酶K消化-饱和酚氯仿法提取外周血白细胞DNA、聚合酶链反应-限制性片段长度多态分析(PCR-RFLP)分别对120例子宫内膜异位症和240例对照组进行基因分型和序列测定。结果病例组MMP-9-1562CC、CT和TT基因型频率分别为81.7%、17.5%和0.8%,对照组分别为75.8%、23.3%和0.8%,两组无统计学差异(P=0.44)。两组CC及CT+TT基因型频率差异也无统计学差异。非条件Logistic回归分析结果显示,携带T等位基因者发生子宫内膜异位症风险是对照组的0.70倍(95%CI=0.40~1.22)。结论MMP-9-1562C>T遗传变异可能与子宫内膜异位症的发病无关。 相似文献
49.
S. Nagassaki R. D. Herculano C. F. O. Graeff J. E. Tanus-Santos 《European journal of clinical pharmacology》2009,65(4):385-392
Purpose Statins have pleiotropic effects, including endothelial nitric oxide synthase (eNOS) upregulation and increased nitric oxide
formation, which can be modulated by a genetic polymorphism in the promoter region of the eNOS gene (T-786C). Here, we report our investigation of whether this polymorphism modulates the effects of atorvastatin on the
fluidity of erythrocyte membranes.
Methods We genotyped 200 healthy subjects (males, 18–60 years of age) and then randomly selected 15 of these with the TT genotype
and 15 with the CC genotype to receive placebo or atorvastatin (10 mg/day oral administration) for 14 days. Cell membrane
fluidity was evaluated by electron paramagnetic resonance (EPR) and spin-labeling method. The EPR spectra were registered
on a VARIAN-E4 spectrometer. Thiobarbituric acid-reactive species (TBA-RS) and plasma membrane cholesterol were determined
in the erythrocytes.
Results Atorvastatin reduced membrane fluidity in CC subjects (P < 0.05) but not in those with the TT genotype (P > 0.05). While no significant differences were found in plasma membrane cholesterol concentrations, higher TBA-RS concentrations
were found in the CC subjects than in the TT subjects (P < 0.05).
Conclusions These findings suggest that a short treatment with atorvastatin is disadvantageous to subjects with the CC genotype for the
T-786C polymorphism compared to those with TT genotype, at least in terms of the hemorheological properties of erythrocytes. 相似文献
50.