全文获取类型
收费全文 | 1172篇 |
免费 | 66篇 |
国内免费 | 5篇 |
专业分类
耳鼻咽喉 | 9篇 |
儿科学 | 13篇 |
妇产科学 | 34篇 |
基础医学 | 202篇 |
口腔科学 | 5篇 |
临床医学 | 92篇 |
内科学 | 202篇 |
皮肤病学 | 3篇 |
神经病学 | 163篇 |
特种医学 | 42篇 |
外科学 | 139篇 |
综合类 | 7篇 |
一般理论 | 1篇 |
预防医学 | 100篇 |
眼科学 | 3篇 |
药学 | 92篇 |
肿瘤学 | 136篇 |
出版年
2024年 | 4篇 |
2023年 | 11篇 |
2022年 | 8篇 |
2021年 | 32篇 |
2020年 | 25篇 |
2019年 | 18篇 |
2018年 | 36篇 |
2017年 | 27篇 |
2016年 | 27篇 |
2015年 | 43篇 |
2014年 | 44篇 |
2013年 | 73篇 |
2012年 | 80篇 |
2011年 | 99篇 |
2010年 | 61篇 |
2009年 | 58篇 |
2008年 | 76篇 |
2007年 | 77篇 |
2006年 | 69篇 |
2005年 | 50篇 |
2004年 | 39篇 |
2003年 | 34篇 |
2002年 | 39篇 |
2001年 | 32篇 |
2000年 | 11篇 |
1999年 | 20篇 |
1997年 | 11篇 |
1996年 | 6篇 |
1995年 | 6篇 |
1994年 | 9篇 |
1993年 | 3篇 |
1992年 | 18篇 |
1991年 | 17篇 |
1990年 | 12篇 |
1989年 | 9篇 |
1988年 | 6篇 |
1987年 | 4篇 |
1986年 | 4篇 |
1985年 | 8篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1981年 | 2篇 |
1979年 | 4篇 |
1977年 | 2篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1973年 | 6篇 |
1972年 | 3篇 |
1971年 | 3篇 |
1970年 | 2篇 |
排序方式: 共有1243条查询结果,搜索用时 31 毫秒
1.
Branislav Radovancevic Alessandro Golino Bojan Vrtovec Cynthia D Thomas Rajko Radovancevic Peggy Odegaard Charles C van Rossem Sebastiaan J M Gaemers William K Vaughn Frank W Smart O H Frazier 《The Journal of heart and lung transplantation》2005,24(6):703-707
BACKGROUND: Left ventricular assist device (LVAD) support is associated with coagulopathy, bleeding, increased blood transfusion, and increased anti-HLA antibody production. Increased anti-HLA antibody production is associated with early transplant rejection, transplant coronary artery disease (CAD), and decreased post-transplant survival rates. We asked whether bridging to transplantation with an LVAD increases the risk of transplant CAD. METHODS: We reviewed data for all adults (>18 years old) who underwent heart transplantation at our institution between 1988 and 2000. After exclusion of transplant recipients who survived <3 years, we divided the remaining cohort into 2 groups: those bridged to transplantation with LVADs (mean duration of support, 149 +/- 107 days, n = 29) and those in United Network for Organ Sharing Status 1 bridged to transplantation without LVADs (controls, n = 86). We compared groups in terms of disease cause, age, sex, donor age, panel-reactive antibody testing, crossmatching, pre- and post-transplant cholesterol concentrations, diagnosis of diabetes mellitus or treated hypertension, infections, calcium channel blocker use, transplant rejection, ischemic time, cytomegalovirus infection, pre-transplant transfusion, and incidence of transplant CAD (defined as any coronary lesion identified by coronary angiography). We considered p < 0.05 to be significant. RESULTS: The bridged and control groups were similar in all respects except mean ischemic time (217 +/- 58 minutes vs 179 +/- 67 minutes, p = 0.007), post-transplant cholesterol concentration (212 +/- 55 mg/dl vs 171 +/- 66 mg/dl, p = 0.007), and pre-transplant transfusion incidence (100% vs 22%, p < 0.001). The incidence of transplant CAD was similar in both groups during a 3-year follow-up period (28% vs 17%, p = 0.238) and during total follow-up (34% vs 35%, p = 0.969). Multivariate logistic regression analysis identified cholesterol concentration at 1 year after transplantation as a significant predictor of CAD at 3 years after heart transplantation (p = 0.0029, odds ratio = 0.984). CONCLUSIONS: Bridging to transplantation with an LVAD does not increase the risk of transplant CAD. Nevertheless, aggressive prophylactic therapy to minimize potential risk factors for transplant CAD, such as increased cholesterol concentration, is warranted in all transplant recipients. 相似文献
2.
Jeroen Kool Sebastiaan M van Liempd Huub van Rossum Danny A van Elswijk Hubertus Irth Jan N M Commandeur Nico P E Vermeulen 《Drug metabolism and disposition》2007,35(4):640-648
A high resolution screening (HRS) technology is described, in which gradient high-performance liquid chromatography (HPLC) is connected on-line to three parallel placed bioaffinity detection systems containing mammalian cytochromes P450 (P450s). The three so-called enzyme affinity detection (EAD) systems contained, respectively, liver microsomes from rats induced by beta-naphthoflavone (CYP1A activity), phenobarbital (CYP2B activity), and dexamethasone (CYP3A activity). Each P450-EAD system was optimized for enzyme, substrate, and organic modifier (isopropyl alcohol, methanol, and acetonitrile) in flow injection analysis mode. Characteristic P450 ligands were used to validate the P450-EAD systems. IC(50) values of the ligands were measured and found to be similar to those obtained with conventional microtiter plate reader assays. Detection limits (n = 3; signal-to-noise ratio = 3) of potent inhibitors ranged from 1 to 3 pmol for CYP1A activity, 4 to 17 pmol for CYP2B activity, and 4 to 15 pmol for CYP3A activity. The three optimized P450-EAD systems were subsequently coupled to gradient HPLC and used to screen compound mixtures for individual ligands. Finally, to increase analysis efficiency, a HRS system was constructed in which all three P450-EAD systems were coupled on-line and in parallel to gradient HPLC. The triple parallelized P450-EAD system was shown to enable rapid profiling of individual components in complex mixtures for inhibitory activity to three different P450s. 相似文献
3.
The effect of dantrolene sodium in relation to blood levels in spastic patients after prolonged administration. 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Journal of neurology, neurosurgery, and psychiatry》网站下载免费的PDF全文](/ch/ext_images/free.gif)
W J Meyler H Bakker J J Kok S Agoston H Wesseling 《Journal of neurology, neurosurgery, and psychiatry》1981,44(4):334-339
In 25 patients with spasticity, pharmacokinetics and effects of dantrolene sodium were investigated after prolonged administration. A beneficial effect occurred in seven patients. The results were better on 100 mg daily than on a higher daily dose. An increase of the daily dose from 200 to 400 mg was not associated with higher blood levels. Many side effects were noted such as: anorexia, nausea, drowsiness, depression and muscle weakness. From this study we conclude that dantrolene sodium is a muscle relaxant with a weak to moderate effect in patients with spasticity; the effect at doses higher than 200 mg daily is probably poor. 相似文献
4.
5.
Keratitis caused by Scedosporium apiospermum successfully treated with a cornea transplant and voriconazole 总被引:2,自引:0,他引:2
下载免费PDF全文
![点击此处可从《Journal of clinical microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Nulens E Eggink C Rijs AJ Wesseling P Verweij PE 《Journal of clinical microbiology》2003,41(5):2261-2264
A case of Scedosporium apiospermum keratitis was successfully treated with oral voriconazole and penetrating keratoplasty. Voriconazole levels in the aqueous humor were 53% of the levels in plasma and exceeded the MIC for the isolate by sevenfold. 相似文献
6.
Cataplexy is usually seen as rapid eye movement (REM) sleep atonia occurring at an inopportune moment. REM sleep atonia is the result of postsynaptic inhibition, i.e. inhibition of alpha motor neurones. Although this may explain the suppression of H-reflexes during REM sleep, cataplexy and laughter, it is not the only explanation. Presynaptic inhibition, in which afferent impulses are prevented from reaching motor neurones, is an alternative. Testing H-reflexes and magnetic-evoked potentials (MEPs) helps to tell them apart: in postsynaptic inhibition MEPs and H-reflexes change in tandem, while H-reflexes may decrease independent of MEPs with other inhibition modes. We studied motor inhibition during laughter, the strongest trigger for cataplexy. H-reflexes were evoked every 2 s in the soleus muscle in 10 healthy subjects watching comical video fragments. MEPs were evoked when H-reflexes decreased during laughter, and, as a control, when subjects did not laugh. Pairs of MEPs and the immediately preceding H-reflexes were studied. Compared with the control condition, laughter caused mean MEP area to increase by 60% (P=0.006) and mean H-reflex amplitude to decrease by 33% (P=0.008). This pattern proves that postsynaptic inhibition cannot have been the sole influence. The findings do not prove which mechanisms are involved; one possibility is that the decrease in H-reflex amplitude was the result of presynaptic inhibition, and that cortical and/or spinal facilitation accounted for increased MEPs. Regardless, the pattern differs fundamentally from the reported mechanism of REM sleep atonia. Existing scanty data on cataplexy suggest a pattern of H-reflexes and MEPs similar to that during laughter, but this needs further study. 相似文献
7.
Rademakers R Melquist S Cruts M Theuns J Del-Favero J Poorkaj P Baker M Sleegers K Crook R De Pooter T Bel Kacem S Adamson J Van den Bossche D Van den Broeck M Gass J Corsmit E De Rijk P Thomas N Engelborghs S Heckman M Litvan I Crook J De Deyn PP Dickson D Schellenberg GD Van Broeckhoven C Hutton ML 《Human molecular genetics》2005,14(21):3281-3292
8.
Role of Toll-like receptor 4 in gram-positive and gram-negative pneumonia in mice 总被引:10,自引:0,他引:10
下载免费PDF全文
![点击此处可从《Infection and immunity》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Branger J Knapp S Weijer S Leemans JC Pater JM Speelman P Florquin S van der Poll T 《Infection and immunity》2004,72(2):788-794
To determine the role of Toll-like receptor 4 (TLR4) in the immune response to pneumonia, C3H/HeJ mice (which display a mutant nonfunctional TLR4) and C3H/HeN wild-type mice were intranasally infected with either Streptococcus pneumoniae (a common gram-positive respiratory pathogen) or Klebsiella pneumoniae (a common gram-negative respiratory pathogen). In cases of pneumococcal pneumonia, TLR4 mutant mice showed a reduced survival only after infection with low-level bacterial doses, which was associated with a higher bacterial burden in their lungs 48 h postinfection. In Klebsiella pneumonia, TLR4 mutant mice demonstrated a shortened survival after infection with either a low- or a high-level bacterial dose together with an enhanced bacterial outgrowth in their lungs. These data suggest that TLR4 contributes to a protective immune response in both pneumococcal and Klebsiella pneumonia and that its role is more important in respiratory tract infection caused by the latter (gram-negative) pathogen. 相似文献
9.
Agrin is a major heparan sulfate proteoglycan accumulating in Alzheimer's disease brain 总被引:4,自引:0,他引:4
下载免费PDF全文
![点击此处可从《The American journal of pathology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Verbeek MM Otte-Höller I van den Born J van den Heuvel LP David G Wesseling P de Waal RM 《The American journal of pathology》1999,155(6):2115-2125
Heparan sulfate proteoglycans (HSPGs) have been suggested to play an important role in the formation and persistence of senile plaques and neurofibrillary tangles in dementia of the Alzheimer's type (DAT). We performed a comparative immunohistochemical analysis of the expression of the HSPGs agrin, perlecan, glypican-1, and syndecans 1-3 in the lesions of DAT brain neocortex and hippocampus. Using a panel of specific antibodies directed against the protein backbone of the various HSPG species and against the glycosaminoglycan (GAG) side-chains, we demonstrated the following. The basement membrane-associated HSPG, agrin, is widely expressed in senile plaques, neurofibrillary tangles and cerebral blood vessels, whereas the expression of the other basement membrane-associated HSPG, perlecan, is lacking in senile plaques and neurofibrillary tangles and is restricted to the cerebral vasculature. Glypican and three different syndecans, all cell membrane-associated HSPG species, are also expressed in senile plaques and neurofibrillary tangles, albeit at a lower frequency than agrin. Heparan sulfate GAG side chains are also associated with both senile plaques and neurofibrillary tangles. Our results suggest that glycosaminoglycan side chains of the HSPGs agrin, syndecan, and glypican, but not perlecan, may play an important role in the formation of both senile plaques and neurofibrillary tangles. In addition, we speculate that agrin, because it contains nine protease-inhibiting domains, may protect the protein aggregates in senile plaques and neurofibrillary tangles against extracellular proteolytic degradation, leading to the persistence of these deposits. 相似文献
10.
E. van der Veur B. S. ten Berge A. J. M. Donker J. F. May F. H. Schuurman H. Wesseling 《European journal of clinical pharmacology》1985,28(5):507-511
Summary After screening two local populations in the northern part of The Netherlands for hypertension, patients with a diastolic pressure (DP) between 95 and 120 mmHg were treated daily either with 50 mg hydrochlorothiazide or 100 mg atenolol. Non-responders were given the combination and if necessary the dose of atenolol was increased to 200 mg. Non-responders to the latter combination were randomized and treated either with 50 mg hydrochlorothiazide and labetalol or with 50 mg hydrochlorothiazide, 200 mg atenolol and prazosin. If after 1 month a DP90 mmHg had been reached the patient was reassessed after a further 3 months. If a DP>90 mmHg was found the dose of labetalol or prazosin was increased and the patient was re-examined after 1 month.This protocol was followed until the maximum dose was reached or adverse reactions prevented a further increase in dosage.During 6 months of treatment there was a further drop in systolic and diastolic blood pressures under both regimens of, respectively, 8.6 and 2.4 mmHg for labetalol, and 7.7 and 5.0 mmHg for the prazosin group. At the end of the period the average daily doses of labetalol and prazosin were 1256 mg and 4.3 mg, respectively. There was no significant difference in the average number of complaints between the labetalol and the prazosin group. 相似文献