全文获取类型
收费全文 | 454篇 |
免费 | 37篇 |
国内免费 | 13篇 |
专业分类
耳鼻咽喉 | 4篇 |
儿科学 | 69篇 |
妇产科学 | 4篇 |
基础医学 | 34篇 |
口腔科学 | 5篇 |
临床医学 | 65篇 |
内科学 | 98篇 |
皮肤病学 | 7篇 |
神经病学 | 11篇 |
特种医学 | 85篇 |
外科学 | 46篇 |
综合类 | 10篇 |
预防医学 | 21篇 |
眼科学 | 2篇 |
药学 | 17篇 |
肿瘤学 | 26篇 |
出版年
2022年 | 2篇 |
2021年 | 6篇 |
2020年 | 2篇 |
2019年 | 2篇 |
2018年 | 2篇 |
2017年 | 2篇 |
2016年 | 6篇 |
2015年 | 10篇 |
2014年 | 13篇 |
2013年 | 14篇 |
2012年 | 11篇 |
2011年 | 5篇 |
2010年 | 8篇 |
2009年 | 12篇 |
2008年 | 10篇 |
2007年 | 20篇 |
2006年 | 7篇 |
2005年 | 13篇 |
2004年 | 4篇 |
2003年 | 8篇 |
2002年 | 9篇 |
2001年 | 2篇 |
2000年 | 5篇 |
1999年 | 16篇 |
1998年 | 24篇 |
1997年 | 21篇 |
1996年 | 28篇 |
1995年 | 24篇 |
1994年 | 15篇 |
1993年 | 11篇 |
1992年 | 10篇 |
1991年 | 11篇 |
1990年 | 12篇 |
1989年 | 17篇 |
1988年 | 16篇 |
1987年 | 13篇 |
1986年 | 16篇 |
1985年 | 9篇 |
1984年 | 8篇 |
1983年 | 12篇 |
1982年 | 9篇 |
1981年 | 5篇 |
1980年 | 10篇 |
1979年 | 9篇 |
1978年 | 8篇 |
1977年 | 3篇 |
1976年 | 7篇 |
1975年 | 7篇 |
1973年 | 5篇 |
1971年 | 2篇 |
排序方式: 共有504条查询结果,搜索用时 0 毫秒
1.
2.
Protective cytotoxic T lymphocyte responses against paramyxoviruses induced by epitope-based DNA vaccines: involvement of IFN-gamma 总被引:1,自引:0,他引:1
Hsu SC; Obeid OE; Collins M; Iqbal M; Chargelegue D; Steward MW 《International immunology》1998,10(10):1441-1447
Plasmid DNA vectors have been constructed with minigenes encoding a single
cytotoxic T lymphocyte (CTL) epitope from either the M2 protein of
respiratory syncytial virus (RSV) or from the nucleoprotein of measles
virus (MV) with or without a signal sequence (also called secretory or
leader sequence). Following intradermal immunization, plasmids in which the
CTL epitopes were expressed in-frame with the signal sequence were more
effective at inducing peptide- and virus- specific CTL responses than
plasmids expressing CTL epitopes without the signal sequence. This
immunization resulted in protection against MV-induced encephalitis and a
significant reduction in viral load following RSV challenge. The reduction
of viral load following RSV challenge was abrogated by prior injection with
anti-IFN-gamma antibodies. These results highlight the ability of
epitope-based DNA immunization to induce protective immune responses to
well-defined epitopes and indicate the potential of this approach for the
development of vaccines against infectious diseases.
相似文献
3.
MW Lieberman R Barrios G Kala SV Kala ED Lykissa CN Ou 《Environmental health perspectives》1999,107(9):A444-A445
Respond on comments on Lieberman's article: Cyclosiloxanes Produce Fatal Liver and Lung Damage in Mice. Environ Health Perspect 107:161-165 相似文献
4.
D C DeVivo M W Haymond M P Leckie Y L Bussman D B McDougal A S Pagliara 《The Journal of clinical endocrinology and metabolism》1977,45(6):1281-1296
A 10 month old female infant was evaluated for severe lactic acidosis. Clinically she was well nourished and had a substantial amount of adipose tissue despite recurrent episodes of acidosis. Her psychomotor development was retarded, her movements were dystonic and generalized seizures punctuated her course. Metabolic abnormalities included elevated blood concentrations of lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, alanine, proline and glycine, decreased blood concentrations of glutamine, aspartate, valine and citrate, and intermittent elevations of serum cholesterol. A trial on a high-fat diet worsened the clinical condition and intensified the ketoacidosis and hyperalaninemia. Analysis of hepatic tissue obtained by open biopsy revealed increased concentrations of lactate, alanine, acetyl-CoA and other short-chain acyl-CoA esters, and decreased concentrations of oxaloacetate, citrate, alpha-ketoglutarate, malate and aspartate. The blood and tissue metabolic perturbations reflected a deficiency of hepatic pyruvate carboxylase. The apparent Km of hepatic citrate synthase for oxaloacetate was 4.6 micrometer. Calculated tissue oxaloacetate concentrations were 0.50--0.84 micrometer suggesting that tricarboxylic acid cycle activity was severely limited by the decreased availability of this substrate. An iv glucose tolerance test resulted in the paradoxical synthesis of ketone bodies. This observation, coupled with the intermittent hypercholesterolemia and the increased tissue acetyl-CoA concentrations, suggests that pyruvate carboxylase is important in modulating the fractional distribution of intracellular acetyl-CoA between the tricarboxylic acid cycle, the beta-hydroxy-beta-methyl-glutaryl-CoA cycle (and the synthesis of cholesterol and ketone bodies), and fatty acid synthesis. Treatment in future cases might be directed toward increasing tissue concentrations of oxaloacetate. 相似文献
5.
M. Homan C. P. Nicholson H. Katz J. Perkins M. Haymond M. Jensen P. Butler R. Rizza 《Diabetologia》1991,34(10):702-708
Summary The metabolic consequences of the prolonged systemic insulin delivery associated with human pancreas transplantation have not been precisely defined. To determine if systemic insulin delivery in the absence of immunosuppressive agents results in alterations in hepatic or extrahepatic insulin action, three groups of dogs were studied 2 months after either a sham operation or after their pancreatic venous drainage was severed and anastomosed to the inferior vena cava or portal vein (sham, peripheral and portal groups, respectively). The pattern of venous drainage was documented by measuring vena cava and portal insulin concentrations before and after glucose injection. Systemic insulin concentrations were higher (p<0.05) in the peripheral group than in the portal group both following a 14-h fast and after intravenous glucose. During a hyperinsulinaemic euglycaemic clamp (1 mU·kg–1·min–1), glucose utilization (measured using [63H] glucose) was slightly lower (p=0.07) in the peripheral than in the portal group. Hepatic glucose release was equal in all groups. Carbon dioxide incorporation into glucose (an estimate of gluconeogenesis) was higher in the portal than peripheral group in the fasted state but not during insulin infusion. Plasma concentrations and flux rates of fatty acids and amino acids did not differ between groups. We conclude that chronic systemic insulin delivery results in a) systemic but not portal hyperinsulinaemia, b) a minimal impairment in insulin-stimulated glucose uptake, without altering insulin-induced suppression of hepatic glucose release, and c) no effect on fatty acid or amino acid turnover. Although chronic systemic insulin delivery appears to have a minimal effect on insulin action, it remains to be determined whether it has other deleterious effects such as enhancing atherogenesis. 相似文献
6.
The effects of recombinant-DNA-derived interferons on the growth of myeloid progenitor cells 总被引:5,自引:0,他引:5
Interferons (IFNs) have been shown to have significant effects on hematopoietic cell growth. Previous studies defining these effects have utilized mouse and human alpha-, beta-, and gamma-IFN isolated from supernatants of stimulated cells. Despite purification, the possible presence of other lymphokines and soluble factors remains a concern. In this study, the effects of gene-cloned alpha- and gamma-IFN on colony- forming units of granulocyte/macrophage (CFU-GM) progenitors cultured from the peripheral blood of normal volunteers were examined. In addition, blast cell colonies from one patient with acute myelogenous leukemia (AML) were studied. The growth of normal CFU-GM and AML blast cell colonies was inhibited in a dose-dependent manner by gamma- and alpha-IFN. gamma-IFN was ten to 100 times more potent than alpha-IFN in that this species of IFN reduced colony formation by greater than 50% at concentrations of less than 15 antiviral U/mL. The effects of gamma- IFN were neutralized by a monoclonal antibody specific for gamma-IFN. These in vitro studies indicate that human gamma-IFN may be an important modulator of myelopoiesis. Although these data indicate a possible efficacy of gamma-IFN in the treatment of AML, the in vitro results should be considered for their in vivo significance. 相似文献
7.
8.
A DNA endonuclease, isolated from the nuclei of normal human and xeroderma
pigmentosum complementation group A (XPA) cells, which recognizes
predominately pyrimidine dimers, was examined for the mechanism by which it
locates sites of damage on UVC-irradiated DNA. In reaction mixtures with
low ionic strengths (i.e. lacking KCl), the normal and XPA endonuclease
locate sites of UV damage on both naked and reconstituted nucleosomal DNA
by different mechanisms. On both of these substrates, the normal
endonuclease acts by a processive mechanism, meaning that it binds
non-specifically to DNA and scans the DNA for sites of damage, whereas the
XPA endonuclease acts by a distributive one, meaning that it randomly
locates sites of damage on DNA. However, while both the normal and XPA
endonucleases can incise UVC irradiated naked DNA, they differ in ability
to incise damaged nucleosomal DNA. The normal endonuclease showed increased
activity on UVC treated nucleosomal DNA compared with naked DNA, whereas
the XPA endonuclease showed decreased activity on the damaged nucleosomal
substrate. Since a processive mechanism of action is sensitive to the ionic
strength of the micro-environment, the KCl concentration of the reaction
was increased. At 70 mM KCI, the normal endonuclease switched to a
distributive mechanism of action and its ability to incise damaged
nucleosomal DNA also decreased. These studies show that there is a
correlation between the ability of these endonucleases to act by a
processive mechanism and their ability to incise damaged nucleosomal DNA;
the normal endonuclease, which acts processively, can incise damaged
nucleosomal DNA, whereas the XPA endonuclease, which acts distributively,
is defective in ability to incise this substrate.
相似文献
9.
Epidemiological evidence indicates that aflatoxin B1 (AFB1) intake is
associated with an increased risk of hepatocellular carcinoma (HCC). The
hepatocarcinogenesis is initiated by covalent binding of AFB1 to cellular
DNA. To determine whether nutritional factors and hormonal status may
influence the binding of AFB1 to hepatic DNA, a cross- sectional study was
performed on a total of 42 male asymptomatic hepatitis B surface antigen
(HBsAg) carriers and 43 male non-carriers in a cohort study on the
multistage development of HCC in Taiwan. The major AFB1-DNA adduct in vivo,
AFB1-N7-guanine, was measured by high- performance liquid chromatography in
urine. Urinary AFB1-N7-guanine was detectable in 40% of the subjects. HBsAg
carriers had a higher detection rate of urinary AFB1-DNA adducts than
non-carriers and the difference was statistically significant after
multivariate adjustment. After taking into account the total AFB1 urinary
metabolite level, chronic HBsAg carrier status, and other potential
confounders, plasma levels of cholesterol, alpha-tocopherol, and alpha- and
beta-carotene were positively associated with the detection rate of the
AFB1-DNA adducts in a dose-dependent manner, whereas plasma lycopene level
was inversely related to the presence of the adducts in urine. The
association of urinary AFB1-DNA adducts with the plasma levels of
cholesterol, alpha-tocopherol, lycopene, and alpha- and beta-carotene was
observed at both low and high exposure levels of AFB1. There was a
synergistic interaction of plasma alpha-tocopherol with alpha- and beta-
carotene on the adduct levels. No association with the adducts was found
for plasma levels of retinol and testosterone. This study demonstrated
different associations of antioxidant vitamins with AFB1- DNA adduct
formation. The data consistent with our previous finding in cultured
woodchuck hepatocytes that alpha-tocopherol and beta-carotene enhanced
AFB1-DNA adduct formation suggest that prospective investigation of the
relationship between plasma micronutrients and risk of AFB1-related HCC is
warranted.
相似文献
10.
LO Larsson MW Bentzon K Berg Kelly L Mellander B-E Skoogh I-L Strannegård A Lind 《Acta paediatrica (Oslo, Norway : 1992)》1994,83(10):1091-1094
We studied 3592 Swedish schoolchildren, 8 or 9 years old, examined for palpable submandibular, cervical and supraclavicular lymph nodes. All children were skin tested with 2 TU PPD RT23 and with 0.1 μ g of Mycobacterium avium sensitin or 0.1 μ g of M. scrofulaceum sensitin. A total of 991 children had palpable lymph nodes in any of the three locations. Among them, 811 had lymph nodes in one location, 162 in two locations and 18 in three. In 312 children, the lymph nodes were ± 5 mm in size in any location. The most common location was submandibular. Boys had a significantly higher prevalence of palpable lymph nodes than girls. There was also seasonal variation. Children infected by atypical mycobacteria (sensitin reaction ±6 mm) did not have a higher prevalence of palpable lymph nodes than those not infected. 相似文献