全文获取类型
收费全文 | 282篇 |
免费 | 22篇 |
国内免费 | 8篇 |
专业分类
儿科学 | 30篇 |
妇产科学 | 3篇 |
基础医学 | 28篇 |
口腔科学 | 10篇 |
临床医学 | 30篇 |
内科学 | 61篇 |
皮肤病学 | 7篇 |
神经病学 | 9篇 |
特种医学 | 61篇 |
外科学 | 16篇 |
综合类 | 8篇 |
预防医学 | 10篇 |
眼科学 | 3篇 |
药学 | 16篇 |
肿瘤学 | 20篇 |
出版年
2021年 | 2篇 |
2020年 | 2篇 |
2019年 | 4篇 |
2018年 | 7篇 |
2017年 | 3篇 |
2016年 | 1篇 |
2015年 | 6篇 |
2014年 | 7篇 |
2013年 | 10篇 |
2012年 | 7篇 |
2011年 | 5篇 |
2010年 | 17篇 |
2009年 | 16篇 |
2008年 | 7篇 |
2007年 | 4篇 |
2006年 | 7篇 |
2005年 | 7篇 |
2004年 | 5篇 |
2003年 | 7篇 |
2002年 | 2篇 |
2001年 | 5篇 |
2000年 | 2篇 |
1999年 | 5篇 |
1998年 | 22篇 |
1997年 | 18篇 |
1996年 | 20篇 |
1995年 | 15篇 |
1994年 | 10篇 |
1993年 | 6篇 |
1992年 | 3篇 |
1991年 | 1篇 |
1990年 | 3篇 |
1989年 | 7篇 |
1988年 | 11篇 |
1987年 | 6篇 |
1986年 | 6篇 |
1985年 | 3篇 |
1984年 | 4篇 |
1982年 | 4篇 |
1981年 | 5篇 |
1980年 | 6篇 |
1979年 | 5篇 |
1978年 | 1篇 |
1977年 | 5篇 |
1976年 | 6篇 |
1975年 | 1篇 |
1948年 | 2篇 |
1932年 | 1篇 |
1925年 | 1篇 |
1924年 | 1篇 |
排序方式: 共有312条查询结果,搜索用时 15 毫秒
81.
Cristina Ferr��s Joachim AF Oude Vrielink Johan WA Verspuy Hein te Riele Anastasia Tsaalbi-Shtylik Niels de Wind 《Molecular therapy》2009,17(8):1373-1380
A substantial fraction of sporadic and inherited colorectal and endometrial cancers in humans is deficient in DNA mismatch repair (MMR). These cancers are characterized by length alterations in ubiquitous simple sequence repeats, a phenotype called microsatellite instability. Here we have exploited this phenotype by developing a novel approach for the highly selective gene therapy of MMR-deficient tumors. To achieve this selectivity, we mutated the VP22FCU1 suicide gene by inserting an out-of-frame microsatellite within its coding region. We show that in a significant fraction of microsatellite-instable (MSI) cells carrying the mutated suicide gene, full-length protein becomes expressed within a few cell doublings, presumably resulting from a reverting frameshift within the inserted microsatellite. Treatment of these cells with the innocuous prodrug 5-fluorocytosine (5-FC) induces strong cytotoxicity and we demonstrate that this owes to multiple bystander effects conferred by the suicide gene/prodrug combination. In a mouse model, MMR-deficient tumors that contained the out-of-frame VP22FCU1 gene displayed strong remission after treatment with 5-FC, without any obvious adverse systemic effects to the mouse. By virtue of its high selectivity and potency, this conditional enzyme/prodrug combination may hold promise for the treatment or prevention of MMR-deficient cancer in humans. 相似文献
82.
YF NGEOW AF WEIL NS KHAIRULLAH MY MOHD YUSOF L LUAM C GAYDOS TC QUINN 《Journal of paediatrics and child health》1997,33(5):422-425
Objective: The incidence of Chlamydia pneumoniae and Chlamydia trachomatis infection was studied among infants and young children admitted to hospital for the management of lower respiratory tract infections, over a 12 month period.
Methodology: Respiratory secretions were examined for chlamydiae by cell culture, enzyme-linked immunosorbent assay and polymerase chain reaction-enzyme immunoassay. Sera were tested by micro-immunofluorescence for chlamydial IgG, IgM and IgA. Other bacterial and viral pathogens were also looked for by standard cultural and serological methods.
Results: Of 87 patients aged 2 months-3 years, an aetiologic diagnosis was made in 41 (47.1%). C. pneumoniae and C. trachomatis were each detected in 1 (1.2%) of the patients. Among common bacterial pathogens, Haemophilus influenzae (13.8%) and Streptococcus pneumoniae (8.1%) were the most frequently identified. Respiratory viruses and elevated Mycoplasma pneumoniae antibodies were found in 10.3% and 9.1% of patients, respectively.
Conclusion: Chlamydiae are infrequent causes of community-acquired acute lower respiratory tract infections in infants and very young children in Malaysia. 相似文献
Methodology: Respiratory secretions were examined for chlamydiae by cell culture, enzyme-linked immunosorbent assay and polymerase chain reaction-enzyme immunoassay. Sera were tested by micro-immunofluorescence for chlamydial IgG, IgM and IgA. Other bacterial and viral pathogens were also looked for by standard cultural and serological methods.
Results: Of 87 patients aged 2 months-3 years, an aetiologic diagnosis was made in 41 (47.1%). C. pneumoniae and C. trachomatis were each detected in 1 (1.2%) of the patients. Among common bacterial pathogens, Haemophilus influenzae (13.8%) and Streptococcus pneumoniae (8.1%) were the most frequently identified. Respiratory viruses and elevated Mycoplasma pneumoniae antibodies were found in 10.3% and 9.1% of patients, respectively.
Conclusion: Chlamydiae are infrequent causes of community-acquired acute lower respiratory tract infections in infants and very young children in Malaysia. 相似文献
83.
84.
85.
Stec I; Wright TJ; van Ommen GJ; de Boer PA; van Haeringen A; Moorman AF; Altherr MR; den Dunnen JT 《Human molecular genetics》1998,7(7):1071-1082
Wolf-Hirschhorn syndrome (WHS) is a malformation syndrome associated with a
hemizygous deletion of the distal short arm of chromosome 4 (4p16.3). The
smallest region of overlap between WHS patients, the WHS critical region,
has been confined to 165 kb, of which the complete sequence is known. We
have identified and studied a 90 kb gene, designated as WHSC1 , mapping to
the 165 kb WHS critical region. This 25 exon gene is expressed ubiquitously
in early development and undergoes complex alternative splicing and
differential polyadenylation. It encodes a 136 kDa protein containing four
domains present in other developmental proteins: a PWWP domain, an HMG box,
a SET domain also found in the Drosophila dysmorphy gene ash -encoded
protein, and a PHD-type zinc finger. It is expressed preferentially in
rapidly growing embryonic tissues, in a pattern corresponding to affected
organs in WHS patients. The nature of the protein motifs, the expression
pattern and its mapping to the critical region led us to propose WHSC1 as a
good candidate gene to be responsible for many of the phenotypic features
of WHS. Finally, as a serendipitous finding, of the t(4;14) (p16.3;q32.3)
translocations recently described in multiple myelomas, at least three
breakpoints merge the IgH and WHSC1 genes, potentially causing fusion
proteins replacing WHSC1 exons 1-4 by the IgH 5'-VDJ moiety.
相似文献
86.
Autosomal recessive retinitis pigmentosa and cone-rod dystrophy caused by splice site mutations in the Stargardt's disease gene ABCR 总被引:12,自引:2,他引:12
Cremers FP; van de Pol DJ; van Driel M; den Hollander AI; van Haren FJ; Knoers NV; Tijmes N; Bergen AA; Rohrschneider K; Blankenagel A; Pinckers AJ; Deutman AF; Hoyng CB 《Human molecular genetics》1998,7(3):355-362
Ophthalmological and molecular genetic studies were performed in a
consanguineous family with individuals showing either retinitis pigmentosa
(RP) or cone-rod dystrophy (CRD). Assuming pseudodominant (recessive)
inheritance of allelic defects, linkage analysis positioned the causal gene
at 1p21-p13 (lod score 4.22), a genomic segment known to harbor the ABCR
gene involved in Stargardt's disease (STGD) and age- related macular
degeneration (AMD). We completed the exon-intron structure of the ABCR gene
and detected a severe homozygous 5[prime] splice site mutation,
IVS30+1G->T, in the four RP patients. The five CRD patients in this
family are compound heterozygotes for the IVS30+1G- >T mutation and a
5[prime] splice site mutation in intron 40 (IVS40+5G- >A). Both splice
site mutations were found heterozygously in two unrelated STGD patients,
but not in 100 control individuals. In these patients the second mutation
was either a missense mutation or unknown. Since thus far no STGD patients
have been reported to carry two ABCR null alleles and taking into account
that the RP phenotype is more severe than the STGD phenotype, we
hypothesize that the intron 30 splice site mutation represents a true null
allele. Since the intron 30 mutation is found heterozygously in the CRD
patients, the IVS40+5G->A mutation probably renders the exon 40 5[prime]
splice site partially functional. These results show that mutations in the
ABCR gene not only result in STGD and AMD, but can also cause autosomal
recessive RP and CRD. Since the heterozygote frequency for ABCR mutations
is estimated at 0.02, mutations in ABCR might be an important cause of
autosomal recessive and sporadic forms of RP and CRD.
相似文献
87.
We report the case of an 8 week old infant with fulminant autoimmune haemolytic anaemia refractory to conventional immunomodulating treatment. Massive haemolysis resulted in cardiac decompensation and acute renal failure which necessitated mechanical ventilation and peritoneal dialysis. Rituximab, a chimeric anti-CD20 monoclonal antibody, halted progression of the haemolytic process, but the patient died of acute viral pneumonia and disseminated fungal infection. Earlier introduction of rituximab might have prevented the renal complications. Paediatricians should be aware of this useful therapeutic tool for treatment of refractory autoimmune haemolytic anaemia and balance its use against the risk of potential life threatening infection. 相似文献
88.
89.
院内感染严重影响重症监护室(ICU)危重病人的治疗。目前5例院内感染病例中就有1例是发生在ICU病房。院内输血感染(blood stream injections,BSIs)使危重病人的监护面临重大挑战。虽然输血感染的死亡率还存在争议,但大量的报道已经证实ICU内菌血症的增多使病人住院时间及费用均有所上升。如一项研究证实患院内菌血症后患者ICU住院期增加〉7天,住院费用额外增加〉2万美元。耐药菌群的不断出现与ICU病人病情加重进一步增加了BSIs的治疗难度。 相似文献
90.
Central giant cell granuloma (CGCG) is a benign lesion of unknown etiology that especially affects the jaws, usually appears in patients younger than 30 years and is more common in females than in males. Lesions generally occur in the anterior portion of the jaws and mandibular lesions frequently cross the midline. The conventional treatment of CGCG is surgical removal. According to clinical and radiological features, the extent of tissue removal ranges from simple curettage to an en bloc resection. We present an 8-year-old male patient, lack of any systemic disease or syndrome, complaining from painless swelling of the left posterior part of the mandible. In intraoral examination, a firm, expansive swelling with overlying intact mucosa, extending from mandibular primary canine to the distal portion of the left permanent first molar, was detected. A panoramic radiograph exhibited an ill-defined radiolucent lesion of 1.5 x 2 cm, extending from left permanent first molar to angulus mandibula and a well-defined, unilocular radiolucent lesion of 1 x 2 cm, extending from angulus to ramus mandibula on the asymptomatic right side. After the assessment of MRI, surgical removal was planned with the otorhinolaryngology department and lesions were totally removed under general anesthesia in two consecutive operation. Histopathologic examination revealed typical giant cell granuloma containing numerous multinucleated giant cells embedded in a fibrous stroma. In presenting this case we aimed to share occurrence of bilateral central giant cell granulomas of the mandible in the absence of hyperparathyroidism and associated syndromes, which is very rare in the literature. 相似文献