全文获取类型
收费全文 | 804篇 |
免费 | 42篇 |
国内免费 | 23篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 14篇 |
妇产科学 | 44篇 |
基础医学 | 136篇 |
口腔科学 | 9篇 |
临床医学 | 58篇 |
内科学 | 202篇 |
皮肤病学 | 2篇 |
神经病学 | 99篇 |
特种医学 | 26篇 |
外科学 | 97篇 |
综合类 | 3篇 |
预防医学 | 47篇 |
眼科学 | 18篇 |
药学 | 53篇 |
中国医学 | 1篇 |
肿瘤学 | 57篇 |
出版年
2023年 | 4篇 |
2022年 | 4篇 |
2021年 | 15篇 |
2020年 | 8篇 |
2019年 | 11篇 |
2018年 | 19篇 |
2017年 | 10篇 |
2016年 | 8篇 |
2015年 | 13篇 |
2014年 | 24篇 |
2013年 | 34篇 |
2012年 | 67篇 |
2011年 | 53篇 |
2010年 | 35篇 |
2009年 | 41篇 |
2008年 | 58篇 |
2007年 | 63篇 |
2006年 | 46篇 |
2005年 | 62篇 |
2004年 | 48篇 |
2003年 | 43篇 |
2002年 | 45篇 |
2001年 | 12篇 |
2000年 | 12篇 |
1999年 | 7篇 |
1998年 | 18篇 |
1997年 | 9篇 |
1996年 | 2篇 |
1995年 | 10篇 |
1994年 | 7篇 |
1993年 | 3篇 |
1992年 | 7篇 |
1991年 | 10篇 |
1990年 | 8篇 |
1989年 | 10篇 |
1988年 | 4篇 |
1987年 | 3篇 |
1986年 | 3篇 |
1984年 | 4篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1981年 | 6篇 |
1980年 | 2篇 |
1977年 | 4篇 |
1976年 | 2篇 |
1973年 | 1篇 |
1968年 | 2篇 |
1964年 | 1篇 |
1959年 | 1篇 |
1948年 | 1篇 |
排序方式: 共有869条查询结果,搜索用时 0 毫秒
1.
Frank A Middleton Marco G Trauzzi Antony E Shrimpton Karen L Gentile Christopher P Morley Helena Medeiros Michele T Pato Carlos N Pato 《American journal of medical genetics. Part B, Neuropsychiatric genetics》2006,(1):28-32
Uniparental isodisomy (iUPD) is a rare genetic condition caused by non-disjunction during meiosis that ultimately leads to a duplication of either the maternal or paternal chromosome in the affected individual. Two types of disorders can result, those due to imprinted genes and those due to homozygosity of recessive disease-causing mutations. Here, we describe the third known case of complete chromosome 4 iUPD of maternal origin. This condition became apparent during whole genome linkage studies of psychiatric disorders in the Portuguese population. The proband is an adult female with normal fertility and no major medical complaints, but a history of major depressive disorder and multiple suicide attempts. The proband's siblings and parents had normal chromosome 4 genotypes and no history of mood disturbance. A brief review of other studies lends support for the possibility that genes on chromosome 4 might confer risk for mood disorders. We conclude that chromosome 4 maternal uniparental disomy (UPD) is a rare disorder that may present with a major depressive phenotype. The lack of a common disease phenotype between this and two other cases of chromosome 4 iUPD [Lindenbaum et al. [1991] Am J Med Genet 49(Suppl 285):1582; Spena et al. [2004] Eur J Hum Genet 12:891-898) would suggest that there is no vital maternal gene imprinting on chromosome 4. However, since there is no reported case of paternal chromosome 4 UPD, paternal gene imprinting on chromosome 4 cannot be excluded. 相似文献
2.
The development of cancer cachexia is perhaps the most common manifestation of advanced malignant diseases and has been recognized as a poor prognostic sign. The abnormalities associated with the condition include progressive weight loss, anorexia, asthenia, and anemia. The degree of cachexia is inversely correlated with the survival time of the patient and always implies a poor prognosis. Currently there is no established mechanism for cancer cachexia, but the severe metabolic disturbances and marked alterations in carbohydrate, lipid, and protein metabolism in the host finally lead to an increased energy deficiency. Weight loss, the key feature of cachexia, is due to a reduction of food intake, an increase in energy expenditure, or a combination of the two. A variety of changes in nutrient metabolism have been described in patients with cancer cachexia. Patients frequently exhibit a relative glucose intolerance and insulin resistance with increased activity of the Cori cycle. The cancer-bearing state affects protein synthesis and breakdown in different tissues of the body in a different manner. An acute-phase protein response can be presented in a significant proportion of patients with cancer with disease progression. A variety of proinflammatory cytokines appears to play a role in aspects of cachexia and a complex network of cytokines in combination with other factors might be involved. Aside from potential humoral mediators of cachexia, tumor-derived biologically active molecules have been reported recently. 相似文献
3.
4.
E J Bromet J E Schwartz S Fennig L Geller L Jandorf B Kovasznay J Lavelle A Miller C Pato R Ram 《Schizophrenia bulletin》1992,18(2):243-255
This article describes the rationale, aims, and methodology of an epidemiological study of psychosis being conducted in Suffolk County, New York. A sample of first-admission patients is drawn from 10 inpatient and 25 outpatient facilities. Diagnostic psychosocial interviews are conducted shortly after admission to treatment, and at 6- and 24-month followup. Consensus diagnoses are made after each interview. Demographic and clinical background characteristics of the first 250 subjects enrolled over a 2-year period are presented here. The response rate was 76 percent. Based on the initial interview, 75 percent of subjects received a diagnosis involving psychosis. The three most common diagnoses were schizophrenia, bipolar disorder with psychotic features, and major depression with psychotic features. Among subjects with psychosis, 58 percent of males and 29 percent of females had a history of substance abuse/dependence. Gender differences were found on several background and clinical characteristics. Males were somewhat younger, less likely to have ever married, and had less education. Although the median length of hospitalization was the same for females and males (27 days), females were more likely to be hospitalized within 1 month of the occurrence of their first psychotic symptom (60% of females compared to 37% of males). Subjects with schizophrenia-related disorders were significantly more impaired on an assessment of negative symptoms than were affectively ill subjects, but clinical ratings of depression were not significantly different across diagnostic groups. 相似文献
5.
Physical mapping of virulence-associated genes in Pseudomonas aeruginosa by transverse alternating-field electrophoresis. 总被引:15,自引:2,他引:13
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)
The relative chromosomal locations of 20 virulence-associated genes in four clinical isolates of Pseudomonas aeruginosa were investigated by using transverse alternating-field electrophoresis. Each strain had a characteristic restriction pattern when digested with either SpeI or DraI and electrophoresed with 15-s pulses. All four strains had restriction fragments that hybridized with each of the gene probes used, although there were variations in fragment size. An SpeI physical map constructed by Ratnaningsih et al. (E. Ratnaningsih, S. Dharmsthiti, V. Krishnapillai, A. Morgan, M. Sinclair, and B. W. Holloway, J. Gen. Microbiol. 136:2351-2357, 1990) for one of these strains, PAO1, was used to identify the location of 11 previously unmapped genes. The physical locations of the remaining genes were found to be consistent with their genetically mapped loci. Whereas phospholipase C and alginate structural and regulatory genes were associated in three separate clusters in the early, middle, and late regions of the chromosome, no virulence cluster was identified. Our data suggest that the pathogenicity of P. aeruginosa results from the gradual acquisition of genes encoding various virulence determinants. 相似文献
6.
Potent inhibition of HIV-1 entry by (s4dU)35 总被引:2,自引:0,他引:2
Horváth A Tokés S Hartman T Watson K Turpin JA Buckheit RW Sebestyén Z Szöllosi J Benko I Bardos TJ Dunn JA Fésüs L Tóth FD Aradi J 《Virology》2005,334(2):214-223
7.
Genetic variants of homocysteine metabolizing enzymes and the risk of coronary artery disease 总被引:2,自引:0,他引:2
Janosíková B Pavlíková M Kocmanová D Vítová A Veselá K Krupková L Kahleová R Krijt J Kraml P Hyánek J Zvárová J Andel M Kozich V 《Molecular genetics and metabolism》2003,79(3):167-175
It is unresolved whether elevated homocysteine in coronary artery disease (CAD) is the cause of arteriosclerosis or its consequence. In contrast, genetic variants of enzymes that metabolize homocysteine cannot be altered by arteriosclerosis. Consequently, their association with CAD would permit to imply causality. We modeled by regression analysis the effect of 11 variants in the methionine cycle upon CAD manifestation in 591 controls and 278 CAD patients. Among the examined variants only the carriership for the c.844ins68 in the cystathionine beta-synthase (CBS) gene was associated with a significantly lowered risk of CAD (OR=0.56; 95% CI=0.35-0.90 in the univariable, and OR=0.41, 95% CI=0.19-0.89 for obese people in the multivariable analysis, respectively). Healthy carriers of the c.844ins68 variant exhibited, compared to the wild type controls, significantly higher postload ratios of blood S-adenosylmethionine to S-adenosylhomocysteine (61.4 vs. 54.9, p=0.001) and of plasma total cysteine to homocysteine (8.6 vs. 7.3, p=0.004). The changes in these metabolites are compatible with an improved methylation status and with enhanced activity of homocysteine transsulfuration. In conclusion, the coincidence of clinical and biochemical effects of a common c.844ins68 CBS variant supports the hypothesis that compounds relating to homocysteine metabolism may play role in the development and/or progression of CAD. 相似文献
8.
Pato CN Macedo A Ambrosio A Vincent JB Bauer A Schindler K Xu J Coelho I Dourado A Valente J Azevedo MH Kennedy JL Pato MT 《American journal of medical genetics》2000,96(6):854-857
We have studied 24 families with multiple affected members with bipolar disorder to test the hypothesis that in those families clinically showing genetic anticipation [Macedo et al., 1999] we would find large repeat expansions. The families meeting inclusion criteria had a minimum of two affected members over two generations and showed marked anticipation both in terms of age of onset and disease severity. We used the repeat expansion detection (RED) method to test patients (n = 24) and controls from these families and unrelated controls (n = 53). We also genotyped patients and family members from two families with large expansions at the known expansion loci on chromosomes 13, 17, and 18. The RED method revealed a higher number of large expansions in patients compared with controls (t-test; P < 0.0055: Mann-Whitney U; P = 0.02). The patients with the largest expansions were typed at the specific loci on chromosomes 13, 17, and 18 and the chromosome 18 expansion locus segregated with disease in one family, and a second family showed segregation with the expansion located at the SCA8 locus on chromosome 13. Genetic anticipation had been analyzed in this cohort of families, with correction for potential ascertainment bias, possible proband effects, cohort effects, regression to the mean, gender effects, and maternal vs. paternal transmission. None of these potential confounds appeared to account for the observed anticipation. We also identified that the presence of large expansions in affected family members derives primarily from two families from the genetically isolated Azores population. One family shows segregation with the chromosome 18 locus, whereas the other family segregates with expansions at the SCA8 locus. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:854-857, 2000. 相似文献
9.
10.
Dina Ruano António Macedo Maria Jo?o Soares José Valente Maria Helena Azevedo Carlos Pato Mara Helena Hutz Clarissa S Gama Maria Inês Lobato Paulo Belmonte-de-Abreu Peter Heutink Joana Almeida Palha 《American journal of medical genetics. Part B, Neuropsychiatric genetics》2007,(5):642-646
Several observations point to the involvement of disturbed lipid biology in schizophrenia. Reduced response to niacin flushing test, which involves vasodilatation induced by prostaglandin D2 (PGD2), is among the evidences, together with decreased CSF levels of lipocalin-type prostaglandin D2 synthase (PTGDS), the enzyme responsible for the synthesis of PGD2 in the brain. Since PTGDS is also a carrier for lipophilic molecules such as retinoids and thyroid hormones, altered PTGDS levels might influence both PGD2-mediated signaling, and vitamin A and thyroid hormone availability. To test whether genetic variants of PTGDS are involved in the etiology of schizophrenia, we searched for variants in the coding and regulatory regions of the gene. We identified four previously described polymorphisms. Using two case-control samples from Portugal and Brazil, none of the polymorphisms tested was associated with the disease. In addition, no transmission distortion was observed in an independent parents-offspring sample from the Azorean Islands. Our data do not support the involvement of the PTGDS gene in the etiology of schizophrenia. 相似文献