首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   500篇
  免费   8篇
  国内免费   3篇
耳鼻咽喉   24篇
儿科学   14篇
妇产科学   4篇
基础医学   40篇
口腔科学   10篇
临床医学   43篇
内科学   105篇
皮肤病学   9篇
神经病学   44篇
特种医学   36篇
外科学   44篇
综合类   5篇
一般理论   1篇
预防医学   21篇
眼科学   1篇
药学   90篇
肿瘤学   20篇
  2023年   3篇
  2022年   2篇
  2021年   4篇
  2020年   4篇
  2019年   4篇
  2018年   6篇
  2017年   2篇
  2016年   8篇
  2015年   7篇
  2014年   14篇
  2013年   25篇
  2012年   31篇
  2011年   36篇
  2010年   13篇
  2009年   23篇
  2008年   22篇
  2007年   36篇
  2006年   23篇
  2005年   25篇
  2004年   24篇
  2003年   18篇
  2002年   23篇
  2001年   18篇
  2000年   13篇
  1999年   11篇
  1998年   12篇
  1997年   11篇
  1996年   10篇
  1995年   13篇
  1994年   6篇
  1993年   7篇
  1992年   8篇
  1991年   3篇
  1990年   4篇
  1989年   4篇
  1988年   9篇
  1987年   5篇
  1986年   1篇
  1985年   4篇
  1984年   4篇
  1983年   4篇
  1982年   5篇
  1981年   3篇
  1980年   1篇
  1977年   1篇
  1976年   1篇
排序方式: 共有511条查询结果,搜索用时 15 毫秒
101.
A case of left knee synovitis scintigraphic imaging is presented in a 66-year-old patient with bilateral knee osteoarthritis and a right knee Baker's cyst, who had undergone a 74 MBq (99m)Tc-pertechnetate intra-articular injection in the right knee. The findings in this case were compared with the intravenously injected methylene disphosphonate technetium-99m ((99m)Tc-MDP) scintigraphic findings and could be interpreted as the result of (99m)Tc-pertechenate through blood communication from the right to the left knee. This case implies that (99m)Tc-pertechnetate may be useful in imaging the synovitis in multiple arthroses even up to 60 min after its administration, instead of the 5 min imaging after the injection of (99m)Tc-MDP.  相似文献   
102.
A woman with a 5-year history of unilateral orofacial granulomatosis required repeated evaluations (including sequential colonoscopies) to establish the diagnosis of cutaneous Crohn's disease, a condition that proved responsive to low doses of oral methotrexate administered weekly. To our knowledge this is the first report describing the use of methotrexate for treatment of orofacial granulomatosis caused by underlying Crohn's disease.  相似文献   
103.
A young male presenting with cutaneous papules and plaques in a segmental distribution in the pelvic girdle area is reported. The clinical features were suggestive of naevus lipomatosus cutaneous superficialis, but diagnostic biopsy is essential to demonstrate the typical histopathological features and exclude important differential diagnoses such as segmental neurofibromatosis.  相似文献   
104.
105.
Colistin penetration into the cerebrospinal fluid (CSF) was studied in five critically ill adult patients receiving colistin methanesulfonate for infections by multiresistant gram-negative bacilli. Colistin concentrations were determined in paired serum and CSF samples, with the latter taken by lumbar puncture, with the exception of one patient with an external ventriculostomy. CSF-to-serum ratios (0.051 to 0.057) for all study patients coincided at all sampling times. The low level (5%) of penetration suggests inadequate bactericidal colistin concentrations in the CSF.Several case reports have described the successful treatment of central nervous system (CNS) infections with colistin (in the form of colistin methanesulfonate [CMS]) administered intravenously and/or either intrathecally or intraventricularly (2, 7-11, 16). However, initial data derived from colistin concentrations measured by microbiological assay suggested poor drug penetration into the cerebrospinal fluid (CSF), which was not enhanced in the presence of meningeal inflammation (5), while more recently, a 25% peak CSF-to-serum concentration ratio (8) and a ∼15% ratio of areas under the CSF/serum concentration-time profiles were reported (9). These findings raise concerns about the effectiveness of intravenous (i.v.) CMS monotherapy. Furthermore, as the data (5, 8, 9) relating to the penetration of colistin into the CSF are based solely on unreliable bioassay measurements, these have to be confirmed by high-performance liquid chromatography, which is now considered to be the only valid approach for quantifying colistin levels (12).In order to determine the CSF penetration of colistin after i.v. administration of CMS, we performed a prospective study of five nonconsecutive critically ill adult patients treated with i.v. CMS for serious gram-negative infections (not necessarily CNS infections) (Table (Table1).1). All patients had CSF withdrawn either for diagnostic reasons (suspected meningitis or ventriculitis) or for the follow-up of a documented CSF infection. The study was approved by the Hospital Ethics and Research Committee and performed in accordance with good clinical practice guidelines. Informed consent was waived.

TABLE 1.

Characteristics of the patients investigateda
Patient no.SexAge (yr)Reason for ICU admissionWeight (kg)Serum creatinine (mg/dl)Infection/pathogen treated with CMSOther antibiotics administeredOutcome
1F40Head injury810.5Ventriculitis/A. baumanniiTigecyclineResponse, sterilization, survival
2F68Head injury671.1Ventriculitis/A. baumanniiMeropenemResponse, sterilization, death unrelated to infection
3M62SAH, intraventricular hemorrhage680.6VAP/A. baumanniiMeropenem, linezolidDeath unrelated to infection
4M36Intracerebral hemorrhage800.8VAP/A. baumanniiMeropenemResponse, survival
5M60SAH74Anuric, CVVHDFBSI/A. baumanniiMeropenemNo response, death
Open in a separate windowaF, female; M, male; ICU, intensive care unit; VAP, ventilator-associated pneumonia; SAH, subarachnoid hemorrhage; BSI, bloodstream infection; CVVHDF, continuous venovenous hemodiafiltration.CMS (colistin; Norma, Athens, Greece) was administered intravenously (100-ml infusion over 30 min). The dosage regimen varied, at the discretion of the attending physician (Table (Table2).2). Samples were collected after at least 2 days of CMS administration, allowing colistin concentrations to reach steady state (with the exception of patient 5 who had rapidly deteriorating renal function). CSF sampling was performed through lumbar puncture, with the exception of patient 1 who had CSF withdrawn through a preexisting external ventriculostomy for hydrocephalus drainage. For patient 1, CSF/serum samples were collected before CMS infusion and at 10 min, 1 h, 2 h, 4 h, 6 h, and 8 h after the end of CMS infusion, while for patients 2, 3, 4, and 5, paired samples were collected at two time points (Table (Table2).2). All samples were immediately transferred on ice to the laboratory, cold centrifuged without delay (1,000 × g, 10 min), and stored at −70°C until analysis by an isocratic high-performance liquid chromatography assay, as previously reported (14). The assay response was linear, between 500 and 5,000 ng/ml for colistin sulfate in sera and between 40 and 1,000 ng/ml in CSF. On a daily basis for the needs of the specific research protocol, the calibration range used for sera was 500 to 2,000 ng/ml and for CSF was 40 to 200 ng/ml. Validation studies included determination of precision, accuracy, and recovery. For the 500-, 1,000-, and 2,000-ng/ml concentrations, intraday and interday variabilities for sera were 6.3, 5.0, and 2.2% and 8.0, 3.8, and 2.9%, respectively, while for the 40-, 80-, and 200-ng/ml concentrations, intraday and interday variabilities for CSF were 5.5, 5.3, and 4.3% and 8.7, 6.2, and 4.9%, respectively. The lower limits of quantification were 80 ng/ml for sera and 40 ng/ml for CSF.

TABLE 2.

Details of CMS dosage, sampling times of biological fluids, and concentrations of colistin in sera and in CSF after i.v. administration
Patient no.CMS regimen (mg/day)Day of CMS treatmentTime of samplingaColistin concn (ng/ml)
Colistin ratio (CSF/sera)
CSFSera
1225/3121 h831,5480.054
2225/3122 h971,8100.054
141 h991,9200.052
3150/262 h438190.053
103 h418020.051
4225/361 h831,5510.054
5Trough428200.051
5150/181 h881,5340.057
8Trough488710.055
Open in a separate windowaTrough, drug concentration measured just before the administration of the next dose.The pharmacokinetic parameters of colistin in sera and CSF were estimated from the concentration-time data of patient 1 by noncompartmental, steady-state analysis using the WinNonlin pharmacokinetic software package (Pharsight Corporation, Mountain View, CA).Characteristics of the patients investigated are presented in Table Table1.1. Patients 1 and 2 had CNS infections (ventriculitis) from Acinetobacter baumannii, while patient 3 had a CNS infection from vancomycin-resistant enterococcus. Patient 2 had received intrathecal colistin, but the last dose had been administered 4 days before CSF sampling, and we assume it did not influence our measurements. On the basis of CSF examination, all three patients with CNS infection had minimal CSF inflammation at the time of sampling. Data on the administered CMS regimen and CSF penetration are presented in Table Table2.2. The concentration-time curves depicting the colistin serum and CSF data of patient 1 are shown in Fig. Fig.1,1, and the estimated pharmacokinetic parameters are shown in Table Table3.3. The ratio of the area under the concentration-time curve (AUC) for CSF to that of sera (AUCCSF/AUCS) was 0.051.Open in a separate windowFIG. 1.Colistin serum and CSF concentrations (ng/ml) versus time profiles under steady-state conditions after three 225-mg doses of CMS in patient 1.

TABLE 3.

Pharmacokinetic parameters of colistin estimated from serum and CSF concentrations at steady state after i.v. administration of CMS in patient 1
Type of samplePharmacokinetic parameters of colistina
Cmax (ng/ml)Cmin (ng/ml)t1/2 (h)CLss (liter/h)Vss (liters)AUC (h·mg/liter)
Sera1,679.3925.611.115.223810.4
CSF90.047.311.70.53
Open in a separate windowaCmax, colistin concentration 10 min after the end of the infusion; Cmin, drug concentration at 8 h; t1/2, elimination half-life; CLss, apparent clearance at steady state calculated as dose/AUC; Vss, apparent volume of distribution at steady state calculated as mean residence time × CLss. For the pharmacokinetic evaluations, the CMS dose was corrected to an equivalent dose of colistin, according to the molecular weight of the two major components, i.e., CMS dose × 1,163/1,743, or CMS dose × 0.667, where 1,163 is the average molecular weight of colistin A and B and 1,743 is the average molecular weight of the respective sodium methanesulfonate salts. Since the precise percentage of colistin A and B, in the batch of CMS administered, was unknown, the precise dose of colistin base could not be estimated with greater accuracy.In patient 1, the concentration-time curves of colistin in sera and CSF ran parallel (with a CSF-to-serum ratio of ∼0.05 at all time points, coinciding with a AUCCSF/AUCS ratio of 0.051 [Table [Table3]),3]), the time to peak levels were the same, and the elimination half-lives were similar in the two biological fluids, in contrast to most other antibiotics, where CSF concentration-time curves usually lag behind those in sera because of their slow entry through the blood-brain barrier (1, 4, 13, 15). However, since the lack of lag time was based on the determination of colistin concentrations in only one patient, this finding needs to be confirmed using a larger number of patients. The ratios of CSF-to-serum concentrations for the five study patients coincided in all cases, despite widely different sampling times, suggesting that the elimination half-lives of colistin in the CSF and sera were similar. Furthermore, in all five patients, the ratios at steady state were equal to the AUCCSF/AUCS ratio of patient 1, indicating that colistin exchange between the central compartment and the CSF is governed by first-order kinetic processes (15).The main finding of our study is that colistin has a CSF penetration of only 5%. This is even less than that shown in previously reported data, based on colistin concentrations determined by bioassay (8, 9). From what we know about colistin pharmacodynamics (6, 12), the levels of colistin measured in the CSF in our study are unlikely to be effective for the eradication of gram-negative bacilli from the CNS. The favorable response of patient 1 could probably be attributed to the coadministration of i.v. tigecycline and, in patient 2, to intrathecal colistin plus i.v. meropenem.Another finding of interest is that no difference in colistin penetration was found between patients with CNS infection (albeit without intense meningeal inflammation [3]) and those without. Indeed, all study patients had minimally inflamed meninges on the day of sampling; therefore, we cannot rule out the possibility that colistin levels in CSF may be higher in patients with bacterial meningitis and intense meningeal inflammation.It is not easy to provide an adequate explanation for the low level of penetration of colistin in the CSF and the corresponding kinetics of this drug in CSF and sera. The very high molecular weight of the drug probably contributes, as it is known that at least for hydrophilic molecules, the rate of diffusion of a molecule into the CSF is inversely proportional to its size (1, 4, 15). The extent of protein binding of colistin (∼60% in a rat animal model [12]) is not expected to affect CSF penetration, while precise data on colistin lipophilicity remain unknown.The shortcomings of our study are that no patient in our series had intense meningeal inflammation and that full concentration-time curves were available only for one patient. Nevertheless, the similar CSF-to-serum concentration ratios at steady state estimated in our study, regardless of sampling time, allow us to be confident that for colistin, even single determinations in CSF and serum samples can provide reliable information on CSF penetration of colistin.Thus, we conclude that colistin penetration to the CSF is very low (∼5%), at least in patients without intense meningeal inflammation. On the basis of this finding, concomitant intrathecal administration of colistin seems warranted for the treatment of CNS infections from gram-negative bacilli.  相似文献   
106.
107.
108.
Malignancy may adversely influence the quality and behaviour of oocytes   总被引:1,自引:1,他引:1  
A case series of eight cycles of in-vitro fertilization (IVF) in five women diagnosed with malignant disorders is presented. These patients chose to defer definitive treatment for a chance for preservation of potential fertility. The response of these patients to ovarian stimulation, and the outcome, was compared with 17 IVF cycles in 12 age- matched patients with isolated tubal infertility. An apparent adverse influence of malignant disease on the quality and behaviour of oocytes was observed. Despite a comparable total number of oocytes per cycle in the two groups, a significantly reduced percentage of mature oocytes was retrieved per cycle from patients with malignant diseases. The oocytes from patients with malignant disorders were of a poorer quality and exhibited a significantly impaired fertilization rate compared to the controls. We propose that neoplastic processes, irrespective of the site or cell of origin, may have a detrimental impact on the biology of oocytes, an effect akin to that seen on spermatozoa in men with certain malignancies.   相似文献   
109.
110.
The quantitative [14C]-2-deoxyglucose autoradiographic method was utilized to assess regional cerebral metabolic rate for glucose (rCMRglc) in rat brain during withdrawal from cocaine self-administration. RCMRglc was determined in 62 regions from brains of naïve rats which were placed into an empty operant chamber for 12 hr continuously, and rats trained to self-administer cocaine during 3 hr training sessions and subsequently placed into the operant chamber for 12 hr continuously with or without access to cocaine. Animals placed into the chamber without access to cocaine were examined 6 hr later, while animals allowed access to the 12 hr cocaine binge were examined either 6 or 72 hr post-cocaine. Metabolic activity was reduced during withdrawal in the nucleus accumbens, olfactory tubercle, islands of Calleja region, basolateral and central amygdaloid nuclei, medial septum, piriform and cingulate cortices, rostral caudatoputamen, entopeduncular nucleus and the adjacent lateral hypothalamus, somatosensory, auditory, and motor cortices compared to the naïve state. These effects were usually more severe at 72 than at 6 hr after binge exposure, with intermediate values observed in cocaine trained animals without binge exposure. The response was negatively correlated with the amount of cocaine consumed during binge exposure in the striatum, olfactory tubercle, piriform, cingulate, somatosensory, and motor cortices. Thus, the amount of cocaine consumed can affect the extent of metabolic depression after sustained drug exposure. The pattern of regional effects suggests that mesolimbic and rostral extrapyramidal dopamine terminal regions and certain of their efferent pathways are preferentially affected during cocaine withdrawal. The reduction of basal metabolic rate observed in these brain regions during cocaine withdrawal may become more severe with time despite the apparent recovery of certain behavioral-motivational responses. © Wiley-Liss, Inc.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号