全文获取类型
收费全文 | 1308篇 |
免费 | 51篇 |
国内免费 | 81篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 68篇 |
妇产科学 | 9篇 |
基础医学 | 138篇 |
口腔科学 | 23篇 |
临床医学 | 229篇 |
内科学 | 303篇 |
皮肤病学 | 36篇 |
神经病学 | 42篇 |
特种医学 | 309篇 |
外科学 | 89篇 |
综合类 | 26篇 |
预防医学 | 30篇 |
眼科学 | 6篇 |
药学 | 71篇 |
肿瘤学 | 60篇 |
出版年
2022年 | 5篇 |
2021年 | 11篇 |
2020年 | 2篇 |
2019年 | 12篇 |
2018年 | 7篇 |
2017年 | 11篇 |
2016年 | 11篇 |
2015年 | 19篇 |
2014年 | 13篇 |
2013年 | 35篇 |
2012年 | 11篇 |
2011年 | 17篇 |
2010年 | 49篇 |
2009年 | 50篇 |
2008年 | 20篇 |
2007年 | 61篇 |
2006年 | 25篇 |
2005年 | 31篇 |
2004年 | 10篇 |
2003年 | 15篇 |
2002年 | 20篇 |
2001年 | 19篇 |
2000年 | 23篇 |
1999年 | 27篇 |
1998年 | 94篇 |
1997年 | 89篇 |
1996年 | 111篇 |
1995年 | 85篇 |
1994年 | 87篇 |
1993年 | 74篇 |
1992年 | 21篇 |
1991年 | 30篇 |
1990年 | 29篇 |
1989年 | 35篇 |
1988年 | 38篇 |
1987年 | 28篇 |
1986年 | 34篇 |
1985年 | 32篇 |
1984年 | 13篇 |
1983年 | 21篇 |
1982年 | 20篇 |
1981年 | 21篇 |
1980年 | 18篇 |
1979年 | 5篇 |
1978年 | 10篇 |
1977年 | 14篇 |
1976年 | 13篇 |
1975年 | 7篇 |
1969年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有1440条查询结果,搜索用时 15 毫秒
71.
Assisted reproductive technology and complex chromosomal rearrangements: the limits of ICSI 总被引:4,自引:0,他引:4
Siffroi JP; Benzacken B; Straub B; Le Bourhis C; North MO; Curotti G; Bellec V; Alvarez S; Dadoune JP 《Molecular human reproduction》1997,3(10):847-851
Complex chromosomal rearrangements are very rare events in the human
population. According to our knowledge on the consequences of simple
reciprocal translocations for male fertility, translocations involving
three or more chromosomes are thought to lead to severe reproductive
impairments in terms of meiotic disturbance or chromosomal imbalance of
gametes. We report the case of a 48 year old man whose sperm count revealed
either oligozoospermia (<10(3) spermatozoa/ml) or azoospermia. He was
referred to the laboratory for in-vitro fertilization after
intracytoplasmic sperm injection. Cytogenetic investigations showed a
complex chromosomal rearrangement involving firstly a translocation between
the short arm of chromosome 7 and the long arm of chromosome 13 and
secondly a translocation between the short arm of the same chromosome 13
and the short arm of chromosome 9. Diagnosis was ascertained by
fluorescence in-situ hybridization and staining of the nucleolar organizer
regions. Theoretical study of the translocated chromosomes predicted a
'chain' configuration of the hexavalent at the pachytene stage of meiosis.
In all, 32 modes of segregation were considered and only one resulted
either in a normal or a balanced gamete karyotype. Genetic counselling and
choice of appropriate artificial reproduction technique are discussed.
相似文献
72.
Peter Henneman Femke van der Sman-de Beer Payman Hanifi Moghaddam Petra Huijts Anton FH Stalenhoef John JP Kastelein Cornelia M van Duijn Louis M Havekes Rune R Frants Ko Willems van Dijk Augustinus HM Smelt 《European journal of human genetics : EJHG》2009,17(5):620-628
Type III hyperlipoproteinemia (HLP) is mainly found in homozygous apolipoprotein (APO) E2 (R158C) carriers. Genetic factors contributing to the expression of type III HLP were investigated in 113 hyper- and 52 normolipidemic E2/2 subjects, by testing for polymorphisms in APOC3, APOA5, HL (hepatic lipase) and LPL (lipoprotein lipase) genes. In addition, 188 normolipidemic Dutch control panels (NDCP) and 141 hypertriglyceridemic (HTG) patients were genotyped as well. No associations were found for four HL gene polymorphisms and two LPL gene polymorphisms and type III HLP. The frequency of the rare allele of APOC3 3238 G>C and APOA5 −1131 T>C (in linkage disequilibrium) was significantly higher in type III HLP patients when compared with normolipidemic E2/2 subjects, 15.6 vs 6.9% and 15.1 vs 5.8%, respectively, (P<0.05). Furthermore, the frequencies of the APOA5 c.56 G>C polymorphism and LPL c.27 G>A mutation were higher in type III HLP patients, though not significant. Some 58% of the type III HLP patients carried either the APOA5 −1131 T>C, c.56 G>C and/or LPL c.27 G>A mutation as compared to 27% of the normolipidemic APOE2/2 subjects (odds ratio 3.7, 95% confidence interval=1.8–7.5, P<0.0001). The HTG patients showed similar allele frequencies of the APOA5, APOC3 and LPL polymorphisms, whereas the NDCP showed similar allele frequencies as the normolipidemic APOE2/2. Patients with the APOC3 3238 G>C/APOA5 −1131 T>C polymorphism showed a more severe hyperlipidemia than patients without this polymorphism. Polymorphisms in lipolysis genes associate with the expression and severity of type III HLP in APOE2/2. 相似文献
73.
Chaperonin-mediated assembly of wild-type and mutant subunits of human propionyl-CoA carboxylase expressed in Escherichia coli 总被引:1,自引:0,他引:1
We developed a bacterial expression system for the human alpha and beta
cDNAs of propionyl-CoA carboxylase (PCC). These cDNAs (less the putative
mitochondrial matrix targeting presequences) were co-expressed in
Escherichia coli on one plasmid vector with each cDNA having its own
IPTG-inducible promoter. Only negligible amounts of active PCC were
measured despite the presence of both alpha and beta subunits as indicated
by Western blot analysis and the almost complete biotinylation of the alpha
subunit. Co-expression of this plasmid with a second plasmid vector
over-expressing the E. coli chaperonin proteins, groES and groEL, resulted
in a several hundred-fold increase in PCC specific activity, to a level
comparable with that found in crude human liver extracts. PCC was partially
purified on monomeric avidin affinity resin and the presence of both alpha
and beta subunits was demonstrated, thereby confirming the assembly of both
subunits into an active enzyme. Deficiency of either alpha PCC or beta PCC
results in propionic acidemia, an autosomal recessive disorder. We used
this expression system to characterize one missense mutation previously
described in five Japanese alleles, namely C1283T (Thr428lle) in beta PCC.
This mutation, when expressed in E.coli under the same conditions as that
of wild-type PCC, had null activity, despite the presence of assembled
alpha PCC and beta PCC subunits. This bacterial expression system can be
useful for analysis of either alpha PCC or beta PCC mutations. Our findings
indicated that the groES and groEL chaperonin proteins were essential for
folding and assembly of the human PCC heteromeric subunits.
相似文献
74.
75.
Lauener RP; Huttner S; Buisson M; Hossle JP; Albisetti M; Seigneurin JM; Seger RA; Nadal D 《Blood》1995,86(4):1400-1407
One mechanism proposed to play a role in T-cell depletion in human immunodeficiency virus (HIV) infection is apoptosis (activation-induced cell death). We assessed whether apoptosis is related to activation of T cells in vivo and its possible triggers. DNA was extracted from peripheral blood mononuclear cells (PBMC) taken from 16 vertically HIV- infected children and 9 HIV-negative children born to HIV-positive mothers (controls) and tested by agarose gel electrophoresis for the presence of DNA fragments specific for apoptosis. Signs of apoptosis were found on in vitro culture of PBMC from 12 of 16 HIV-infected children, but not in PBMC from the nine controls. Eleven of the 12 HIV- infected children with apoptosis showed an elevated (> 15%) proportion of CD3+/HLA-DR+ cells. This was due to an increased proportion of CD8+/HLA-DR+ cells, as shown in 7 of 7 further tested patients. In none of the probands an increased (> 5%) proportion of IL-2 receptor expressing CD3+ cells was found. T cells undergoing apoptosis were preferentially of the CD8+ phenotype. Expansion of circulating CD8+/interleukin-2 receptor (IL-2R)-/HLA-DR+ T cells is known to occur during active infection with herpes viruses. To investigate the possible role of herpes viral coinfections for apoptosis in HIV infection, we focused on Epstein-Barr virus (EBV) as an example for a herpes virus usually acquired during childhood. In 10 of 12 patients with apoptosis, we found increased levels of EBV genome in PBMC and/or tissues, indicating active EBV replication. By contrast, no increased burden of EBV was found in the four HIV-infected patients without apoptosis or in the controls. Our data indicate that in children the occurrence of apoptosis in HIV infection is closely related to activation of CD8+ T cells. Furthermore, primoinfection with or reactivation of herpes viruses, such as EBV, may substantially contribute to such T-cell activation and the ensuing apoptosis. Additional studies are warranted to evaluate the contribution of herpes virus-triggered apoptosis to the T-cell loss leading to the acquired immunodeficiency syndrome. 相似文献
76.
Jolanda MA Boer Jan Albert Kuivenhoven Edith JM Feskens Evert G Schouten Louis M Havekes Jacob C Seidell John JP Kastelein Daan Kromhout 《Clinical genetics》1999,56(2):158-163
We investigated interactions between a mutation (D9N) in the lipoprotein lipase (LPL) gene and physical activity, as well as other lifestyle factors, on lipid traits in a population-based sample of Dutch men and women (n = 379). We used questionnaire information to classify physical activity, alcohol consumption, and smoking habits, while overweight was defined as a body mass index (BMI) > 25 kg/m2. Non-fasting blood samples were used for the determination of lipid traits and the D9N genotype. Fifteen subjects (4%) carried the mutation. They presented with higher levels of total cholesterol, apolipoprotein (apo) B and triglycerides compared to non-carriers. While no interactions with overweight, alcohol consumption, and smoking were found, a strong interaction between the D9N mutation and physical activity became apparent. Physically inactive D9N carriers (n = 5) had considerably higher total cholesterol (+2 mmol/l, p < or = 0.0001) and apo B levels (+63 mg/dl, p < or = 0.0001) compared to non-carriers of this mutation, whereas their high-density lipoprotein (HDL)-cholesterol concentrations were lower (-0.22 mmol/l, p < 0.05). This was not the case for physically active D9N carriers (n = 10). In conclusion, a common variant of the LPL gene (D9N) adversely affects plasma lipid and lipoprotein profiles. However, the unfavorable consequences may be counteracted by physical activity. 相似文献
77.
JD Roberts JC Herkert J Rutberg SM Nikkel ACP Wiesfeld D Dooijes RM Gow JP van Tintelen MH Gollob 《Clinical genetics》2013,83(5):452-456
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease that predominantly affects the right ventricle and is associated with ventricular arrhythmias that may lead to sudden cardiac death. Mutations within at least seven separate genes have been identified to cause ARVC, however a genetic culprit remains elusive in approximately 50% of cases. Although negative genetic testing may be secondary to pathogenic mutations within undiscovered genes, an alternative explanation may be the presence of large deletions or duplications involving known genes. These large copy number variants may not be detected with standard clinical genetic testing which is presently limited to direct DNA sequencing. We describe two cases of ARVC possessing large deletions involving plakophilin‐2 (PKP2) identified with microarray analysis and/or multiplex ligation‐dependent probe amplification (MLPA) that would have been classified as genotype negative with standard clinical genetic testing. A deletion of the entire coding region of PKP2 excluding exon 1 was identified in patient 1 and his son. In patient 2, MLPA analysis of PKP2 revealed deletion of the entire gene with subsequent microarray analysis demonstrating a de novo 7.9 Mb deletion of chromosome 12p12.1p11.1. These findings support screening for large copy number variants in clinically suspected ARVC cases without clear disease causing mutations following initial sequencing analysis. 相似文献
78.
79.
José GM Hofhuis Henk F van Stel Augustinus JP Schrijvers Johannes H Rommes Jan Bakker Peter E Spronk 《Critical care (London, England)》2009,13(1):118-3
During recent years increasing attention has been given to the quality of survival in critical care. Health-related quality
of life (HRQOL) is an important issue both for patients and their families. Furthermore, admission to the intensive care unit
can have adverse psychological effects in critically ill patients. Recent studies conducted in critically ill patients have
measured HRQOL. However, usually absent from such reports are evaluations of conceptual issues, addressing factors such as
why HRQOL should be measured in critically ill patients, how to define and standardize domains of HRQOL, whether proxies can
provide useful information about HRQOL in critically ill patients, whether response shift occurs in critically ill patients,
and whether post-traumatic stress disorder (PTSD) occurs in critically ill patients. Some studies reported moderate agreement
between patients and their proxies, although lower levels of agreement may be reported for psychosocial or physical functioning.
Response shift (adaptation and change in perception) appears to be an important phenomenon and likely to be present, but it
is seldom measured when estimating HRQOL in critically ill patients. Furthermore, vigilance for symptoms of PTSD and early
interventions to prevent PTSD are needed. 相似文献
80.