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41.
Cocaine is a major risk factor for antipsychotic induced akathisia, parkinsonism and dyskinesia 总被引:1,自引:0,他引:1
Objective: To assess the relative contribution of different drugs of abuse to extrapyramidal side effects (EPS) of antipsychotic drugs. Method: 106 consecutively contacted or admitted male patients in the Psychiatric Center of Surinam (PCS) with schizophrenia or a related disorder were included. Prevalence and severity of EPS were measured with the Unified Parkinson's Disease Rating Scale (UPDRS), the Abnormal Involuntary Movement rating Scale (AIMS), the Barnes Akathisia Rating Scale (BARS) and the Dystonia rating scale. Recent use of cigarettes, cannabis, alcohol, and cocaine were assessed. Standard multiple regression analyses were used to evaluate the relative contribution of above-mentioned drugs of abuse controlled for milligrams haloperidol equivalent a day and use of anticholinergic medication. Results: Recent cocaine use was significantly associated with severity of dyskinesia (p = 0.001), parkinsonism (p = 0.007), and akathisia (p < 0.001) (n = 106). Conclusions: Recent cocaine use is a major risk factor for antipsychotic induced EPS. 相似文献
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43.
Hon YY; Fessing MY; Pui CH; Relling MV; Krynetski EY; Evans WE 《Human molecular genetics》1999,8(2):371-376
The molecular basis for the genetic polymorphism of thiopurine S -
methyltransferase (TPMT) has been estab-lished for Caucasians, but it
remains to be elucidated in African populations. In the current study, we
determined TPMT genotypes in a population of 248 African-Americans and
compared it with allele frequencies in 282 Caucasian Americans. TPMT
genotype was determined in all individuals with TPMT activity indicative of
a heterozygous genotype (</=10.1 U/ml pRBC, n = 23African- Americans, n
= 21 Caucasians) and a control group with TPMT activity indicative of a
homozygous wild-type genotype (>10.2 U/ml pRBC, n = 23
African-Americans, n = 21 Caucasians). No mutant alleles were found in the
high activity control groups. The overall mutant allele frequencies were
similar in African-Americans and Caucasians (4.6 and 3.7% of alleles,
respectively). However, while TPMT*3C was the most prevalent mutant allele
in African-Americans (52.2% of mutant alleles), it represented only 4.8% of
mutant alleles in Caucasians ( P < 0.001). In contrast, TPMT*3A and
TPMT*2 were less common in African-Americans (17.4 and 8.7% of mutant
alleles), whereas TPMT*3A was the most prevalent mutant allele in
Caucasians (85.7% of mutant alleles). A novel allele ( TPMT*8 ), containing
a single nucleotide transition (G644A), leading to an amino acid change at
codon 215 (Arg-->His), was found in one African-American with
intermediate activity. These data indicate that the same TPMT mutant
alleles are found in American black and white populations, but that the
predominant mutant alleles differ in these two ethnic groups.
相似文献
44.
MH Sun G Mechtersheimer P Moellera CH Herfarth MV Knebel Doeberitz HK Scharkert T Lehnert J Gebert 《World journal of gastroenterology : WJG》2000,6(3)
AIM To study the clonality of the esophageal carcinosarcoma by using molecular approaches.METHODS Two esophageal carcinosarcomas were included in the study. Tumor area from dysplasticlesion, squamout cell carcinoma, basaloid cell carcinoma and spindle cell elements were microdissectedseparately. Each element was analyzed with 14 microsatellite markers and direct sequenced for p53 gene andras gene mutation.RESULTS Both tumors displayed a typical histologic feature of carcinosarcoma. Both cases showed thedivergent differentiation by immunohistochemistry study. In case 1 the identical LOH at p53 and hMLH1 lociwas detected. The heterogenous LOH was detected only in carcinosarcoma at RB1 and BRCA1 loci, whilethe LOH at ACTC locus was seen only in sarcoma. The same mutation of the splice site of exon 6-intron 6displayed in the two tumor elements. In case 2, a coordinate LOH at RB locus was demonstrated in threetypes of tumor elements: sqamous carcinoma, basaloid carcinoma and spindle cell element. A heterogenousLOH was seen only in spindle cells at TAP1 locus. No mutation in exon 5-8 of p53 gene has been found incase 2. No mutation of K-ras gene was found.CONCLUSION Although the different differentiation, the two elements of esophageal carcinosarcoma mayhave a single clonality. The p53 gene mutation occurred before the two differentiation directions switched.The distinct molecular genotype can be determined through molecular biological analysis. The microsatelliteprofiling can serve as an approach to find out which genetic alteration occurs before or after thedifferentiation is determines. 相似文献
45.
46.
LINKED ARTICLES
This is a rebuttal by the authors (Green et al., pp. 1523–1536 of this issue) to a commentary by Parrott, pp. 1518–1520 of this issue. To view the article by Green et al. visit http://dx.doi.org/10.1111/j.1476-5381.2011.01819.x. To view the commentary by Parrott visit http://dx.doi.org/10.1111/j.1476-5381.2012.01941.xWe thank Prof Parrott (Parrott 2012) for his interest in our review (Green et al., 2012). Our main aim was to discuss the problems that arise in interpreting data obtained when administering 3,4-methylenedioxymethamphetamine (MDMA) to experimental animals in terms of possible clinical consequences and vice versa, not to disparage the evidence that Ecstasy is neurotoxic in humans. We presented evidence that the pharmacokinetics of MDMA in rats and primates are fundamentally different from the pharmacokinetics of the drug in humans. Because the plasma half-life of the drug in rats is 10 times shorter than in humans, the acute adverse events in rats may be minimal compared with those in humans, and this includes body temperature and endocrine changes. Conversely, the rapid metabolism of the drug in rats to form neurotoxic metabolites may result in more severe long-term effects in that species than those that may occur in humans.We had no intention of suggesting that there was no evidence for some recreational Ecstasy users presenting with evidence of 5-HT neurotoxicity, albeit it is clear from the literature that some of this evidence remains open to several interpretations. What we did claim was that pure 3,4-methylenedioxymethamphetamine (MDMA) taken alone was unlikely to cause 5-HT neurotoxicity in man. Here we must emphasize the term MDMA, as it is crucial to our discussion. Parrott, in contrast, uses the term ‘Ecstasy/MDMA’ several times when discussing neurotoxicity (Parrott, 2012). This association of Ecstasy with MDMA is one of the major problems of translation that we addressed. The Ecstasy tablet that most recreational users buy and ingest is not necessarily MDMA. Indeed, in many cases, it clearly is not. The tablet is often adulterated with other compounds, and one investigation identified no less than 14 substances other than MDMA in Ecstasy tablets, which users nevertheless presumably believed contained only MDMA (Vogels et al., 2009). Many of the adulterants identified were also psychoactive and included compounds structurally related to MDMA such as 3,4-methylenedioxyethylamphetamine and 2-methylamino-1-(3,4-methylenedioxyphenyl)butane, which have poorly researched pharmacology and toxicology. In addition, most recreational users of Ecstasy also knowingly ingest other psychoactive compounds such as alcohol and cannabis. Alcohol, for example, alters the pharmacokinetics of MDMA (Hamida et al., 2009). While, as Parrott states, clinical studies have attempted to allow for these confounding factors in any examination of the physical and psychological effects of MDMA in humans, such analysis is always limited not only by the other compounds the evaluators are unaware of, but also drugs perhaps not even considered to be relevant by the user and therefore not disclosed. It is unlikely that coffee and ‘energy drinks’ such as Red Bull are always disclosed, but there is now good preclinical evidence that caffeine, which incidentally has also been found as an adulterant in Ecstasy tablets, enhances both the hyperthermia and neurotoxicity induced in rats by MDMA (Camarasa et al., 2006; Vanattou-Saïfoudine et al., 2010). And this brings us to the crux of the problem and weakness of all the clinical data cited by Parrott (2012). A basic tenet of all good clinical pharmacology is accurate knowledge of the doses administered, frequency of administration and any confounding factors such as other drugs being consumed. None of these data are available with any precision in the clinical studies quoted. Of course one has some indication as to dose (although as Vogels et al., (2009) reported, the dose contained in illicitly obtained tablets is highly variable) and frequency of drug ingestion, but this information is generally obtained from the user whose recall is likely to be limited or who decides to obfuscate. Crucially, the information can never take into account the problem of drug tablet adulteration. The fact that hair or urine samples detect MDMA merely shows the user has consumed the drug, not how much or when or what other drugs were taken concurrently.We never suggested that MDMA exposure was not going to be associated with physical or psychological change. However such changes are not necessarily associated with long-term neurotoxic damage. We have shown that long-term behavioural effects can occur in rats both with and without 5-HT neurotoxicity (Fone et al., 2002; Bull et al., 2003; Rodsiri et al., 2011). It is interesting that Parrott approvingly quotes the Verheyden et al. (2003) study in support of his contention that neurotoxic damage has occurred. Because this study noted that the majority of persons reporting chronic psychiatric problems reported ‘improved mental health’ after quitting the drug, this surely allows us to conclude that the drug had produced subacute changes rather than any that could be associated with long-term neurotoxic damage.A further limitation to any clinical study is that one cannot perform prospective studies with the aim of investigating whether long-term neurotoxic events occur, so weaknesses arise with regard to any psychological abnormalities observed. Are persons with high risk of psychiatric problems more likely to misuse the drug, or does the drug induce changes in high-risk individuals? If high risk also happened to be associated with 5-HT abnormalities in the brains, then any conclusion that MDMA has induced neurotoxicity is spurious.We most certainly did not suggest that MDMA acted as a neurotoxin only under conditions of severe hyperthermia as is stated by Parrot in his sixth paragraph (Parrott, 2012). We have been involved in many studies on the effects of MDMA on body temperature in rats (see Docherty and Green, 2010) including one that demonstrated that neurotoxicity can occur in the absence of hyperthermia (O''Shea et al., 1998) and another that showed that hyperthermia worsens neurotoxic damage (Green et al., 2004). In our review, what we did propose was that because of the very different pharmacokinetics of MDMA in rats and humans, it is probable that humans would suffer serious or fatal adverse events at plasma levels below those likely to be required to induce 5-HT neurotoxicity.We emphasize again that we are not denying the clinical observations reviewed by Parrott, but conclude that the effects seen cannot be ascribed solely to the effects of MDMA, as he seems to be proposing. We also repeat our contention that MDMA in combination with other drugs may induce neurotoxicity and this could be said to be supported by the clinical studies quoted by Parrott.Finally, we can but assume that Parrott concurs with our principal conclusion that ‘the doses currently being used to investigate the possible therapeutic benefits of MDMA are unlikely to produce any severe acute or importantly any long-term neurotoxic damage in the human brain’ as he used such a dose (100 mg or approximately 1.4 mg·kg −1) in one of his recent studies in human volunteers (Parrott et al., 2011). 相似文献47.
Arranz Arija Já Cassinello Espinosa J Climent Durán Má Rivero Herrero F 《Clinical & translational oncology》2012,14(7):520-527
Prostate cancer (PC) is the most common cancer in men. Many patients have prolonged survival and die of other diseases, so treatment decisions are often influenced by age and coexisting comorbidities. The main procedure to diagnose PC is an ultrasound-guided core needle biopsy, which is indicated when a digital rectal examination (DRE) finds nodularity or when PSA is >10 ng/ml, but is also recommended with PSA between 4.0 and 10 ng/ml. Depending on age, PSA, Gleason score and characteristics of the tumour, treatment options for localised PC are active surveillance, radical prostatectomy and radiation therapy. Androgen deprivation treatment (ADT) should be added to radiotherapy for men with intermediate- or high-risk PC. ADT is the current standard first-line treatment for metastatic PC. Castration-resistant PC is a heterogeneous entity. Several treatments such as sipuleucel-T, docetaxel-based chemotherapy, radium 223, cabazitaxel or abiraterone plus prednisone, zoledronic and denosumab, are useful for this situation. 相似文献
48.
Empar Valdivieso Cristina Rey Marisa Barrera Victoria Arija Josep Basora Josep Ramon Marsal TAB_ES Study Group 《BMC public health》2010,10(1):665
Background
Over the last decade notable progress has been made in developed countries on monitoring smoking although experimenting with cigarettes and smoking in young people remains a serious public health problem. This paper reports a cross-sectional study at the beginning of the 3-year follow-up community study TA_BES. The aim was to study the prevalence of smoking in addition to determining predictive factors for when smoking commences in a representative population of 12-year-old first year compulsory secondary education students. 相似文献49.
The use of systemic antimicrobials in the treatment of acute and chronic periodontal diseases must be viewed as a dilemma. On the one hand, the approach is attractive because of the microbial nature of periodontal diseases but, on the other hand, evidence of benefit of these agents is equivocal for the majority of periodontal diseases and antimicrobials have the potential to cause harm. The disadvantages of systemic antimicrobials can be grouped under the headings of allergic reactions, superinfection, toxicity, drug interactions, patient compliance and, perhaps of most widespread importance, bacterial resistance. Mechanical debridement methods, including drainage of pus for acute periodontal abscesses, should be considered the first line treatment for most periodontal diseases. Systemic antimicrobials should be considered as adjuncts to mechanical debridement methods and, in chronic disease, never used alone as they can predispose to abscess formation. Adjunctive systemic antimicrobials may be considered in acute disease where debridement or drainage of pus is difficult, where there is local spread or systemic upset. In chronic periodontal diseases, adjunctive antimicrobials should be considered in early onset or rapidly progressive disease or in advanced chronic adult disease where mechanical therapies have failed or surgery is not a preferred option. Inadequate oral hygiene and tobacco smoking are contra-indications to the use of antimicrobials. The value of systemic antimicrobials, where other systemic risk factors co-exist, has still to be established. The role of microbial diagnosis and sensitivity testing for antimicrobial selection at this time must be questioned. 相似文献
50.