全文获取类型
收费全文 | 870篇 |
免费 | 32篇 |
国内免费 | 67篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 38篇 |
妇产科学 | 9篇 |
基础医学 | 60篇 |
口腔科学 | 8篇 |
临床医学 | 148篇 |
内科学 | 79篇 |
皮肤病学 | 13篇 |
神经病学 | 20篇 |
特种医学 | 137篇 |
外科学 | 18篇 |
综合类 | 26篇 |
预防医学 | 43篇 |
眼科学 | 1篇 |
药学 | 332篇 |
肿瘤学 | 36篇 |
出版年
2022年 | 4篇 |
2021年 | 10篇 |
2018年 | 5篇 |
2016年 | 9篇 |
2015年 | 11篇 |
2014年 | 11篇 |
2013年 | 23篇 |
2012年 | 20篇 |
2011年 | 20篇 |
2010年 | 27篇 |
2009年 | 34篇 |
2008年 | 26篇 |
2007年 | 67篇 |
2006年 | 27篇 |
2005年 | 20篇 |
2004年 | 17篇 |
2003年 | 24篇 |
2002年 | 17篇 |
2001年 | 13篇 |
2000年 | 10篇 |
1999年 | 25篇 |
1998年 | 44篇 |
1997年 | 37篇 |
1996年 | 29篇 |
1995年 | 29篇 |
1994年 | 29篇 |
1993年 | 24篇 |
1992年 | 22篇 |
1991年 | 23篇 |
1990年 | 25篇 |
1989年 | 32篇 |
1988年 | 28篇 |
1987年 | 18篇 |
1986年 | 20篇 |
1985年 | 19篇 |
1984年 | 16篇 |
1983年 | 9篇 |
1982年 | 16篇 |
1981年 | 11篇 |
1980年 | 14篇 |
1979年 | 13篇 |
1978年 | 13篇 |
1977年 | 14篇 |
1976年 | 11篇 |
1975年 | 17篇 |
1974年 | 3篇 |
1973年 | 4篇 |
1972年 | 7篇 |
1971年 | 5篇 |
1970年 | 7篇 |
排序方式: 共有969条查询结果,搜索用时 15 毫秒
11.
The effects of acute and chronic stages of carrageenan-induced air-pouch inflammation on the pharmacokinetics of prednisolone were studied in male Wistar rats. Chronic inflammation produced a significant increase in the area under the curve (AUC) of prednisolone compared to control animals (6594 ± 2144 vs 3530 ± 2164 µg · hr/ L). The effect of acute inflammation was not significant (AUC = 4996 ± 3813). Both acute and chronic inflammation also reduced thein vitro plasma protein binding of prednisolone, the reduction being much greater after chronic inflammation. The AUC of free prednisolone after chronic inflammation was 3141 µg · hr/L, compared to 1121 µg · hr/L in the control group and 1823 µg · hr/L after acute inflammation. The mean values of half-life and apparent volume of distribution at steady-state in each group were similar. These results indicate that prednisolone must be used with caution in the treatment of inflammatory diseases because of higher free concentrations of the steroid. 相似文献
12.
Michael WJ Hii Robert N Gibson Anthony G Speer Neil A Collier Noel Sherson Cate Jardine 《Journal of Medical Imaging and Radiation Oncology》2003,47(4):393-403
We reviewed the results of percutaneous intervention of hilar biliary malignancy over a 10‐year period at a single institution: the Royal Melbourne Hospital. Ninety‐nine patients (100 treated in total) were included. Information was retrieved by retrospective examination of patient notes and radiology, combined with interviews with family and relevant physicians. Sixty‐nine patients were treated with insertion of semipermanent stents, 19 had external drain tubes, and 25 received percutaneous access for Iridium brachytherapy. Adequate drainage was achieved in 87% of the patients stented, and percutaneous access was successful in 96% of patients planned for brachytherapy. Of those patients undergoing endoprosthesis insertion, early complications occurred in 39% and late complications in 23%. Average survival for the entire patient population was 227.3 days, with a median of 167 days. Longer survival times (213 vs 142 days) and lower complication rates (44 vs 64%) are observed with metal stents in comparison with plastic stents. Percutaneous intervention is an important treatment option in hilar biliary malignancy, particularly in patients unfit for surgery. Reasonable survival with good palliation is the most common outcome, and most patients do not require further intervention. 相似文献
13.
14.
Isolation and characterization of propagable cell lines (HUNC) from the androgen-sensitive Dunning R3327H rat prostatic adenocarcinoma 总被引:1,自引:0,他引:1
Presnell SC; Borchert KM; Glover WJ; Gregory CW; Mohler JL; Smith GJ 《Carcinogenesis》1998,19(4):585-590
The Dunning H rat prostate tumor (R3327H) is a widely used experimental
model of human prostatic adenocarcinoma (CaP). The Dunning H tumor has been
characterized as androgen-sensitive, androgen-receptor (AR) positive,
prostate-specific antigen and prostatic acid phosphatase (PAP) positive. To
date, the tumor has been maintained by serial passage in vivo because of
the lack of an in vitro cell line that retains the characteristics of the
in vivo tumor. The objective of the present study was to establish a
propagable cell line from R3327H adenocarcinoma that maintained androgen
sensitivity and expression of AR, PSA and PAP. Tissue harvested from an in
vivo R3327H tumor was dissociated with collagenase and placed into
Richter's improved media (with supplements). A cytokeratin-positive
epithelial cell line (HUNC- E) and a vimentin-positive stromal cell line
(HUNC-S) were generated from the primary culture, subcultured continuously
for >300 days, and passaged >50 times. Survival of the HUNC-E cell
line in vitro depended on several media supplements, including
nicotinamide, insulin, transferrin, selenium and epidermal growth factor
(EGF). HUNC-E cells expressed AR and produced PSA and PAP throughout the
culture period, as confirmed by immunocytochemistry and Western blot
analyses. Addition of 14 nM testosterone (T) or dihydrotestosterone (DHT)
to HUNC-E cells, stimulated DNA synthesis as well as anchorage-independent
growth and PSA production, which demonstrated the androgen-sensitive nature
of the cells in vitro. When HUNC-E and HUNC-S cells were combined in a 3:1
ratio and introduced subcutaneously into syngeneic male hosts, tumors
formed in 2/3 animals with an average latency of 7 months. RT-PCR and
immunocytochemical characterization of the HUNC cell lines revealed that
the cells expressed several growth factors and their cognate receptors,
including HGF, TGF-alpha and the TGF-betas, indicating the establishment of
potential autocrine loops in the neoplastic cells. The HUNC-E and HUNC-S
CaP cell lines, which retain the characteristics of the epithelial and
stromal components of the in vivo R3327H tumor, will allow a more thorough
and informative molecular and biological analysis of prostatic
adenocarcinoma.
相似文献
15.
16.
James Q. Rose Anthony M. Yurchak William J. Jusko 《Journal of pharmacokinetics and pharmacodynamics》1981,9(4):389-417
Six healthy male volunteers were given 5, 20, and 50 mg of oral prednisone and 5, 20, and 40 mg doses of intravenous prednisolone. Plasma and urine concentrations of prednisone and prednisolone were determined by HPLC, and the binding of prednisolone to plasma proteins was measured by radioisotopic and equilibrium dialysis techniques. The pharmacokinetics of both oral prednisone and intravenous prednisolone were dose-dependent. The mean oral dose plasma clearances of prednisone ranged from 572 ml/min/ 1.73 m
2
for the 5mg dose to 2271 ml/min/1.73 m
2
for the 50 mg dose. Changes in prednisone half-life were insignificant, but increases in the half-life of its metabolite were dose-dependent. The systemic plasma clearance of i.v. prednisolone was dose-dependent and increased from 111 to 194 ml/min/1.73 m
2
over the 5 to 40 mg i.v. dosage range. The steady-state volume of distribution also increased, but little change in mean transit time and half-life was found. The binding of prednisolone to plasma proteins was markedly concentration-dependent, and a two compartment, nonlinear equation was used to characterize the effective binding of prednisolone to transcortin and albumin. The apparent pharmacokinetic parameters of protein-free and transcortin-free prednisolone were relatively constant with dose. The interconversion of prednisone and prednisolone varied with time and dose, although prednisolone concentrations dominated by 4-to 10-fold over prednisone. In urine, 2–5% of either administered drug was excreted as prednisone and 11–24% as prednisolone. The apparent renal clearances of both steroids were also nonlinear and unrelated to protein binding. These studies indicate that the pharmacokinetics of prednisone and prednisolone are dose-dependent and that protein binding does not fully explain their apparent nonlinear distribution and disposition.This work was supported in part by Grant 24211 from the National Institutes of General Medical Sciences, National Institutes of Health. 相似文献
17.
Arianne C Lim Kitty WM Bloemenkamp Kees Boer Johannes J Duvekot Jan Jaap HM Erwich Tom HM Hasaart Pieter Hummel Ben WJ Mol Jos PM Offermans Charlotte M van Oirschot Job G Santema Hubertina CJ Scheepers Willem A Schöls Frank PHA Vandenbussche Maurice GAJ Wouters Hein W Bruinse 《BMC pregnancy and childbirth》2007,7(1):1-6
Background
Adequate vitamin D concentrations during pregnancy are necessary to neonatal calcium homeostasis, bone maturation and mineralization. The aim of study is to evaluate serum vitamin D concentrations in mothers and their newborns and effect of vitamin D deficiency on pregnancy outcomes.Methods
552 pregnant women were recruited from Tehran University educating hospitals in the winter of 2002. Maternal and cord blood samples were taken at delivery. The serum was assayed for 25-hydroxyvitamin D3, calcium, phosphorus and parathyroid hormone.Results
The prevalence of vitamin D deficiency in maternal and cord blood samples were 66.8% and 93.3%, respectively (<35 nmol/l). There was significant correlation between maternal and cord blood serum concentrations of vitamin D. In mothers with vitamin D deficiency, cord blood vitamin D concentrations was lower than those from normal mothers (P = .001). Also, a significant direct correlation was seen between maternal vitamin D intake and weight gain during pregnancy.Conclusion
Consideration to adequate calcium and vitamin D intake during pregnancy is essential. Furthermore, we think it is necessary to reconsider the recommendation for vitamin D supplementation for women during pregnancy. 相似文献18.
Clinical features and serum antinuclear antibodies in 230 Danish patients with systemic sclerosis 总被引:5,自引:2,他引:5
Jacobsen S; Halberg P; Ullman S; Van Venrooij WJ; Hoier-Madsen M; Wiik A; Petersen J 《Rheumatology (Oxford, England)》1998,37(1):39-45
The objective was to investigate the relationship between the presence of
different types of antinuclear antibodies (ANA) in patients with systemic
sclerosis (SSc) and the presence of clinical features. Sera from 230
patients with SSc were tested for the presence of ANA, including
anticentromere antibodies (ab), antitopoisomerase I ab, anti- U1 RNP ab and
antinucleolar ab, including anti-Th RNP, anti-U3 RNP and anti-U17 RNP.
Clinical features were registered prospectively in a clinical database.
Eighty-two per cent of the patients were women. The median age was 58 yr
(45-67, quartiles) and median age at disease onset was 44 (30-55) yr. ANA
were found in 86% of the patients (anticentromere: 34%; antitopoisomerase
I: 14%; anti-U1 RNP: 6.5%; antinucleolar total: 16%; anti-Th RNP: 2.2%;
anti-U3 RNP: 3.5%; anti- U17 RNP: 0%). Anticentromere ab were found to be
related to a high prevalence of calcinosis, telangiectasia, digital ulcers,
acrosclerosis, primary biliary cirrhosis, isolated reduction of pulmonary
diffusing capacity, and a low prevalence of radiological evidence of
pulmonary fibrosis. Antitopoisomerase I ab were associated with a high
prevalence of digital joint deformity, distal osteolysis, radiological
signs of pulmonary fibrosis, a low prevalence of calcinosis and late onset
of disease. Anti-U1 RNP ab were related to a high prevalence of arthritis
and myositis, a low prevalence of calcinosis, and early disease onset. The
presence of antinucleolar ab, including anti-U3 RNP and anti-Th RNP, was
not significantly related to any particular clinical features in this
study; possibly due to the small number of patients with these ab. The
presence of anticentromere, antitopoisomerase I and anti-U1 RNP ab in the
serum was also found to have previously described clinical correlations in
a group of Danish SSc patients.
相似文献
19.
Jacqueline AM Smith DL Patil OT Daniels Y-S Ding J-D Gallezot S Henry KHS Kim S Kshirsagar WJ Martin GP Obedencio E Stangeland PR Tsuruda W Williams RE Carson ST Patil 《The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)》2015,18(2)
Background:
Monoamine reuptake inhibitors exhibit unique clinical profiles that reflect distinct engagement of the central nervous system (CNS) transporters.Methods:
We used a translational strategy, including rodent pharmacokinetic/pharmacodynamic modeling and positron emission tomography (PET) imaging in humans, to establish the transporter profile of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor.Results:
TD-9855 was a potent inhibitor of norepinephrine (NE) and serotonin 5-HT uptake in vitro with an inhibitory selectivity of 4- to 10-fold for NE at human and rat transporters. TD-9855 engaged norepinephrine transporters (NET) and serotonin transporters (SERT) in rat spinal cord, with a plasma EC50 of 11.7ng/mL and 50.8ng/mL, respectively, consistent with modest selectivity for NET in vivo.Accounting for species differences in protein binding, the projected human NET and SERT plasma EC50 values were 5.5ng/mL and 23.9ng/mL, respectively. A single-dose, open-label PET study (4–20mg TD-9855, oral) was conducted in eight healthy males using the radiotracers [11C]-3-amino-4- [2-[(di(methyl)amino)methyl]phenyl]sulfanylbenzonitrile for SERT and [11C]-(S,S)-methylreboxetine for NET. The long pharmacokinetic half-life (30–40h) of TD-9855 allowed for sequential assessment of SERT and NET occupancy in the same subject. The plasma EC50 for NET was estimated to be 1.21ng/mL, and at doses of greater than 4mg the projected steady-state NET occupancy is high (>75%). After a single oral dose of 20mg, SERT occupancy was 25 (±8)% at a plasma level of 6.35ng/mL.Conclusions:
These data establish the CNS penetration and transporter profile of TD-9855 and inform the selection of potential doses for future clinical evaluation. 相似文献20.
Dal Canto Elisa Remmelzwaal Sharon van Ballegooijen Adriana Johanne Handoko M. Louis Heymans Stephane van Empel Vanessa Paulus Walter J. Nijpels Giel Elders Petra Beulens Joline WJ 《Heart failure reviews》2022,27(1):207-218
Heart Failure Reviews - This study aimed to evaluate the diagnostic performance of echocardiographic markers of heart failure with preserved ejection fraction (HFpEF) and left ventricular diastolic... 相似文献