全文获取类型
收费全文 | 637篇 |
免费 | 70篇 |
专业分类
耳鼻咽喉 | 5篇 |
儿科学 | 12篇 |
妇产科学 | 25篇 |
基础医学 | 117篇 |
口腔科学 | 37篇 |
临床医学 | 79篇 |
内科学 | 162篇 |
皮肤病学 | 9篇 |
神经病学 | 24篇 |
特种医学 | 13篇 |
外科学 | 59篇 |
综合类 | 3篇 |
预防医学 | 25篇 |
眼科学 | 4篇 |
药学 | 55篇 |
肿瘤学 | 78篇 |
出版年
2019年 | 4篇 |
2018年 | 7篇 |
2017年 | 4篇 |
2016年 | 4篇 |
2015年 | 7篇 |
2014年 | 13篇 |
2013年 | 21篇 |
2012年 | 29篇 |
2011年 | 21篇 |
2010年 | 18篇 |
2009年 | 18篇 |
2008年 | 26篇 |
2007年 | 25篇 |
2006年 | 22篇 |
2005年 | 31篇 |
2004年 | 17篇 |
2003年 | 30篇 |
2002年 | 26篇 |
2001年 | 14篇 |
2000年 | 28篇 |
1999年 | 25篇 |
1998年 | 12篇 |
1997年 | 7篇 |
1996年 | 4篇 |
1995年 | 11篇 |
1993年 | 6篇 |
1992年 | 17篇 |
1991年 | 23篇 |
1990年 | 20篇 |
1989年 | 13篇 |
1988年 | 11篇 |
1987年 | 8篇 |
1986年 | 9篇 |
1985年 | 23篇 |
1984年 | 9篇 |
1983年 | 10篇 |
1981年 | 7篇 |
1980年 | 7篇 |
1979年 | 7篇 |
1978年 | 8篇 |
1977年 | 12篇 |
1976年 | 8篇 |
1975年 | 15篇 |
1974年 | 11篇 |
1973年 | 9篇 |
1972年 | 7篇 |
1971年 | 12篇 |
1968年 | 8篇 |
1967年 | 4篇 |
1966年 | 3篇 |
排序方式: 共有707条查询结果,搜索用时 11 毫秒
81.
Sprong T Pickkers P Geurts-Moespot A van der Ven-Jongekrijg J Neeleman C Knaup M Leroy D Calandra T van der Meer JW Sweep F van Deuren M 《Shock (Augusta, Ga.)》2007,27(5):482-487
Macrophage migration inhibitory factor (MIF) is a mediator of innate immunity and important in the pathogenesis of septic shock. Lipopolysaccharide (LPS) and tumor necrosis factor (TNF) alpha are reported to be inducers of MIF. We studied MIF and cytokines in vivo in patients with meningococcal disease, in human experimental endotoxemia, and in whole blood cultures using a newly developed sensitive and specific enzyme-linked immunosorbent assay. Twenty patients with meningococcal disease were investigated. For the human endotoxemia model, 8 healthy volunteers were intravenously injected with 2 ng/kg Escherichia coli LPS. Whole blood from healthy volunteers was incubated with LPS or heat-killed meningococci. Macrophage migration inhibitory factor concentration in blood was increased during meningococcal disease and highest in the patients presenting with shock compared with patients without shock. Plasma concentration of MIF correlated with disease severity, the presence of shock and with the cytokines interleukin (IL) 1beta, IL-10, IL-12, and vascular endothelial growth factor, but not with TNF-alpha. MIF was not detected in blood in experimental endotoxemia, nor after stimulation of whole blood with LPS or meningococci, although high levels of TNF-alpha were seen in both models. In conclusion, MIF is increased in patients with meningococcal disease and highest in the presence of shock. Macrophage migration inhibitory factor cannot be detected in a human endotoxemia model and is not produced by whole blood cells incubated with LPS or meningococci. 相似文献
82.
We compared apo A-I isolated from the lipoproteins of the Golgi apparatus of rat liver with apo A-I found in plasma lipoproteins. Golgi apo A-I consists of 3 main isoforms with a molecular weight of approximately 28000 and isoelectric points (pI) of 5.97, 5.88 and 5.76, respectively. Plasma apo A-I consists of 4 major and 3 minor isoforms with a molecular weight of 27000. The pI of the major isoforms (numbered 4-7) is 5.88, 5.80, 5.70 and 5.60, respectively. In order to investigate which of the plasma isoforms derived directly from Golgi apo A-I, [35S]methionine was injected into the portal vein and Golgi and plasma apo A-I were isolated shortly thereafter. While all Golgi isoforms were labelled only 3 isoforms of plasma apo A-I (namely isoforms 5, 6 and 7) were found to be labelled. The major plasma isoform (isoform 4 which accounts for more than 60% of apo A-I mass of plasma HDL) was found to be unlabelled. However, when 35S plasma lipoproteins newly secreted by the liver were incubated in vitro in the presence of heparinized plasma, labelled isoform 4 appeared suggesting that heparinized plasma contained some factor capable of converting isoforms 5-7 into isoform 4. This plasma factor appears to be a protease as the in vitro formation of isoform 4 is prevented by protease inhibitors. 相似文献
83.
84.
85.
E H Charreau A Attramadal P A Torjesen K Purvis R Calandra V Hansson 《Molecular and cellular endocrinology》1977,6(4-5):303-307
Specific receptors for [125I]hPrl (human prolactin) are present in membrane preparations of rat testis. The receptors are specific for lactogenic hormones (prolactin and human growth hormone) but do not bind gonadotropins. The prolactin receptors are localized exclusively in the interstitial cell tissue, and are not present in membrane preparations from isolated seminiferous tubules. The localization of prolactin receptors interstitial tissue suggests that the effect of prolactin on LH/hCG-stimulated testosterone production is due to a direct effect of prolactin of Leydig cells. 相似文献
86.
Deiana L Garuti R Pes GM Carru C Errigo A Rolleri M Pisciotta L Masturzo P Cantafora A Calandra S Bertolini S 《Arteriosclerosis, thrombosis, and vascular biology》2000,20(1):236-243
One of the genetic features of the Sardinian population is the high prevalence of hemoglobin disorders. It has been estimated that 13% to 33% of Sardinians carry a mutant allele of the alpha-globin gene (alpha-thalassemia trait) and that 6% to 17% are beta-thalassemia carriers. In this population, a single mutation of beta-globin gene (Q39X, beta(0) 39) accounts for >95% of beta-thalassemia cases. Because previous studies have shown that Sardinian beta-thalassemia carriers have lower total and low density lipoprotein (LDL) cholesterol than noncarriers, we wondered whether this LDL-lowering effect of the beta-thalassemia trait was also present in subjects with familial hypercholesterolemia (FH). In a group of 63 Sardinian patients with the clinical diagnosis of FH, we identified 21 unrelated probands carrying 7 different mutations of the LDL receptor gene, 2 already known (313+1 g>a and C95R) and 5 not previously reported (D118N, C255W, A378T, T413R, and Fs572). The 313+1 g>a and Fs572 mutations were found in several families. In cluster Fs572, the plasma LDL cholesterol level was 5.76+/-1.08 mmol/L in subjects with beta(0)-thalassemia trait and 8.25+/-1.66 mmol/L in subjects without this trait (P<0.001). This LDL-lowering effect was confirmed in an FH heterozygote of the same cluster who had beta(0)-thalassemia major and whose LDL cholesterol level was below the 50th percentile of the distribution in the normal Sardinian population. The hypocholesterolemic effect of beta(0)-thalassemia trait emerged also when we pooled the data from all FH subjects with and without beta(0)-thalassemia trait, regardless of the type of mutation in the LDL receptor gene. The LDL-lowering effect of beta(0)-thalassemia may be related to (1) the mild erythroid hyperplasia, which would increase the LDL removal by the bone marrow, and (2) the chronic activation of the monocyte-macrophage system, causing an increased secretion of some cytokines (interleukin-1, interleukin-6, and tumor necrosis factor-alpha) known to affect the hepatic secretion and the receptor-mediated removal of apolipoprotein B-containing lipoproteins. The observation that our FH subjects with beta(0)-thalassemia trait (compared with noncarriers) have an increase of blood reticulocytes (40%) and plasma levels of interleukin-6 (+60%) supports these hypotheses. The lifelong LDL-lowering effect of beta(0)-thalassemia trait might slow the development and progression of coronary atherosclerosis in FH. 相似文献
87.
S G Mendoza H Carrasco A Zerpa Y Briceno F Rodriguez J Speirs C J Glueck 《Metabolism: clinical and experimental》1991,40(4):368-377
In 17 men, aged 27 to 54 years, with myocardial infarction 2 to 10 months before the current exercise study, we aimed to determine whether 3 months of exercise training, at a level designed to elevate high-density lipoprotein cholesterol (HDLC), would be associated with changes in endogenous sex steroid hormones and postheparin lipoprotein and hepatic lipases, and whether the changes in sex hormones, lipids, lipoproteins, apolipoproteins, and physical activity were interrelated. Supervised bicycle ergometry, 30 minutes, 3 days per week, eliciting 75% of maximum heart rate, produced a significant training effect, with a 26% increase in the duration of the exercise test at a standardized, submaximal workload (P less than or equal to .001), and a reduction in heart rate measured at a standardized submaximal workload, P = .08. After 3 months' training, mean HDLC increased 23% (30 to 37 mg/dL), P less than or equal to .001, mean apo A2 increased 19% (43 to 51 mg/dL), P less than or equal to .001, and the ratio of total cholesterol (TC) to HDLC decreased 26% (P less than or equal to .01), while estradiol (E2) levels decreased 45% (50.1 to 27.8 pg/mL), P less than or equal to .0001. After 1 and 2 months' exercise, TC (12% [P less than or equal to .001], 11% [P less than or equal to .01]), and low-density lipoprotein cholesterol (LDLC) (13% [P less than or equal to .01], 12% [P less than or equal to .01]) were reduced. Hepatic lipase decreased 16% (P less than or equal to .01) and 16% (P less than or equal to .05) after 1 and 3 months' exercise. There were no significant changes in apo A1, lipoprotein lipase, testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), or weight. By stepwise regression analysis, after 3 months' training, 66% (P = .0025) of the variance for the increase in HDLC from baseline to day 90 was accounted for independently by a decrease in triglyceride (F = 13.2, P = .003), by reduced heart rate on a fixed submaximal load (F = 12.7, P = .0035), and by a decrease in hepatic lipase (F = 5.5, P = .036). A modest, achievable exercise program can have significant cardiovascular benefit for men after myocardial infarction by ameliorating their hyperestrogenemia, reducing TC and LDLC, improving the TC to HDLC ratio, and elevating HDLC and apo A2. The increment in HDLC was related independently to improved capacity to sustain submaximal exercise and to exercise-induced reductions in triglyceride and postheparin hepatic lipase. 相似文献
88.
Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist 总被引:2,自引:20,他引:2 下载免费PDF全文
Liles WC Broxmeyer HE Rodger E Wood B Hübel K Cooper S Hangoc G Bridger GJ Henson GW Calandra G Dale DC 《Blood》2003,102(8):2728-2730
Stromal cell-derived factor 1 (SDF1/CXCL12) and its cognate receptor, CXCR4, play key regulatory roles in CD34+ cell trafficking. We investigated whether AMD3100, a selective CXCR4 antagonist, could mobilize hematopoietic progenitor cells from marrow to peripheral blood in healthy human volunteers. Initially, 10 persons each received a single dose of AMD3100 (80 microsubcutaneously), which induced rapid, generalized leukocytosis associated with an increase in peripheral blood CD34+ cells, representing pluripotent hematopoietic progenitors by in vitro colony-forming unit assays, from 3.8 +/- 0.5/microL to 20.7 +/- 3.5/microL at 6 hours. Subsequent dose-response studies showed a maximum increase in circulating CD34+ cells from 2.6 +/- 0.3/microL to 40.4 +/- 3.4/microL at 9 hours after 240 micro/kg AMD3100. Serial administration of AMD3100 (80 microg/kg/d for 3 days) resulted in consistent, reversible increases in peripheral blood CD34+ cells. AMD3100 was well tolerated and caused only mild, transient toxicity. These findings suggest potential clinical application of AMD3100 for CD34+ cell mobilization and collection for hematopoietic stem cell transplantation. 相似文献
89.
T Calandra J D Baumgartner G E Grau M M Wu P H Lambert J Schellekens J Verhoef M P Glauser 《The Journal of infectious diseases》1990,161(5):982-987
Serum concentrations of immunoreactive tumor necrosis factor/cachectin (TNF), interleukin-1 beta (IL-1 beta), interferon-gamma (IFN gamma), and interferon-alpha (IFN alpha) were prospectively measured in 70 patients with septic shock to determine their evolution and prognostic values. In a univariate analysis, levels of TNF (P = .002) and IL-1 beta (P = .05) were associated with the patient's outcome, but not IFN alpha (P = .15) and IFN gamma (P = .26). In contrast, in a stepwise logistic regression analysis, the severity of the underlying disease (P = .01), the age of the patient (P = .02), the documentation of infection (nonbacteremic infections vs. bacteremias, P = .03), the urine output (P = .04), and the arterial pH (P = .05) contributed more significantly to prediction of patient outcome than the serum levels of TNF (P = .07). After 10 days, the median concentration of TNF was undetectable (less than 100 pg/ml) in the survivors, whereas it remained elevated (305 pg/ml, P = .002) in the nonsurvivors. Thus, in patients with septic shock due to various gram-negative bacteria, other parameters than the absolute serum concentration of immunoreactive TNF contributed significantly to the prediction of outcome. 相似文献
90.
OBJECTIVE:. To describe a case of vaccine associated paralytic poliomyelitis (VAPP) and relate this to current UK immunization policy. METHOD: A case report in which the clinical course and factors leading to the diagnosis are described and then related to reports of paralytic poliomyelitis in the literature. RESULTS: The child in this case was left severely disabled by paralytic poliomyelitis. The pathological process was related to a pararectal abscess needing urgent drainage shortly after immunisation. CONCLUSION: The skeletal muscle damage due to the presence of the pararectal abscess may have acted as the 'provocation' in the development of poliomyelitis. Adoption of a policy of initial vaccination by the parenteral route as in the USA and European countries has been shown to greatly reduce this risk. The UK could adopt this policy which would minimise the risk of VAPP, as all recorded paralytic poliomyelitis in the UK in the last decade has been vaccine related. 相似文献