全文获取类型
收费全文 | 421篇 |
免费 | 22篇 |
国内免费 | 18篇 |
专业分类
耳鼻咽喉 | 7篇 |
儿科学 | 15篇 |
妇产科学 | 5篇 |
基础医学 | 32篇 |
口腔科学 | 21篇 |
临床医学 | 45篇 |
内科学 | 103篇 |
皮肤病学 | 8篇 |
神经病学 | 9篇 |
特种医学 | 51篇 |
外科学 | 60篇 |
综合类 | 13篇 |
预防医学 | 33篇 |
眼科学 | 3篇 |
药学 | 29篇 |
肿瘤学 | 27篇 |
出版年
2023年 | 3篇 |
2022年 | 5篇 |
2021年 | 2篇 |
2020年 | 3篇 |
2019年 | 5篇 |
2018年 | 8篇 |
2017年 | 5篇 |
2016年 | 3篇 |
2015年 | 8篇 |
2014年 | 6篇 |
2013年 | 16篇 |
2012年 | 13篇 |
2011年 | 15篇 |
2010年 | 25篇 |
2009年 | 20篇 |
2008年 | 20篇 |
2007年 | 25篇 |
2006年 | 15篇 |
2005年 | 10篇 |
2004年 | 13篇 |
2003年 | 13篇 |
2002年 | 12篇 |
2001年 | 10篇 |
2000年 | 9篇 |
1999年 | 9篇 |
1998年 | 15篇 |
1997年 | 14篇 |
1996年 | 16篇 |
1995年 | 10篇 |
1994年 | 13篇 |
1993年 | 11篇 |
1992年 | 3篇 |
1991年 | 5篇 |
1990年 | 4篇 |
1989年 | 9篇 |
1988年 | 13篇 |
1987年 | 10篇 |
1986年 | 12篇 |
1985年 | 13篇 |
1984年 | 7篇 |
1983年 | 6篇 |
1982年 | 6篇 |
1981年 | 4篇 |
1980年 | 4篇 |
1979年 | 3篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1975年 | 4篇 |
排序方式: 共有461条查询结果,搜索用时 31 毫秒
1.
R. P. Heaney T. M. Zizic I. Fogelman W. P. Olszynski P. Geusens C. Kasibhatla N. Alsayed G. Isaia M. W. Davie C. H. Chesnut III 《Osteoporosis international》2002,13(6):501-505
Risedronate treatment reduces the risk of vertebral fracture in women with existing vertebral fractures, but its efficacy
in prevention of the first vertebral fracture in women with osteoporosis but without vertebral fractures has not been determined.
We examined the risk of first vertebral fracture in postmenopausal women who were enrolled in four placebo-controlled clinical
trials of risedronate and who had low lumbar spine bone mineral density (BMD) (mean T-score =–3.3) and no vertebral fractures at baseline. Subjects received risedronate 5 mg (n= 328) or placebo (n= 312) daily for up to 3 years; all subjects were given calcium (1000 mg daily), as well as vitamin D supplementation (up
to 500 IU daily) if baseline serum 25-hydroxyvitamin D levels were low. The incidence of first vertebral fracture was 9.4%
in the women treated with placebo and 2.6% in those treated with risedronate 5 mg (risk reduction of 75%, 95% confidence interval
37% to 90%; P= 0.002). The number of patients who would need to be treated to prevent one new vertebral fracture is 15. When subjects were
stratified by age, similar significant reductions were observed in patients with a mean age of 64 years (risk reduction of
70%, 95% CI 8% to 90%; P= 0.030) and in those with a mean age of 76 years (risk reduction of 80%, 95% CI 7% to 96%; P= 0.024). Risedronate treatment therefore significantly reduces the risk of first vertebral fracture in postmenopausal women
with osteoporosis, with a similar magnitude of effect early and late after the menopause.
Received: 12 September 2001 / Accepted: 11 December 2001 相似文献
2.
D. Agnusdei G. Crepaldi G. Isaia G. Mazzuoli S. Ortolani M. Passeri L. Bufalino C. Gennari 《Calcified tissue international》1997,61(2):142-147
One hundred ninety-eight postmenopausal women (aged 50–65 years) with vertebral bone density (VBD) 1 SD below the mean value
for normal, age-matched, postmenopausal subjects were enrolled in six Italian centers and 134 completed 2 years of treatment.
All subjects were randomly allocated to a 2-year treatment with oral ipriflavone (200 mg t.i.d.) or a matching placebo, according
to a double-blind, parallel group design. All patients also received an oral daily calcium supplement of 1 g as calcium carbonate.
VBD and markers of bone turnover were measured at baseline, and every 6 months. A complete routine analysis of liver and kidney
functions along with hematological parameters were measured before and at the end of treatment period. The valid completers
analysis showed a significant increase of VBD in ipriflavone-treated women with average percent changes of +1.4 after 1 year,
and +1% at the end of treatment period (P < 0.05). The placebo group presented a significant decrease of VBD after 2 years of treatment (P < 0.05). The difference between treatments was significant (P < 0.01). The intention to treat analysis confirmed the significant decrease of VBD in the placebo group, with no changes
in ipriflavone-treated women. Skeletal ALP significantly decreased in ipriflavone-treated women (P < 0.05). Serum BGP and urine HOP/Cr showed a significant decrease only in ipriflavone-treated women, suggesting an inhibitory
effect on bone turnover rate. Adverse reactions, mainly gastrointestinal, occurred to a similar extent in the two treatment
groups. The evaluation of patients' compliance, assessed by residual tablets count, revealed a drug intake of more than 80%
after 2 years in 92.5% and 92.8% of patients treated with ipriflavone or placebo, respectively. This study demonstrates that
ipriflavone can prevent bone loss in postmenopausal women with low bone mass.
Received: 1 April 1996 / Accepted: 5 March 1997 相似文献
3.
Bone mineral content (BMC) and testosterone levels were evaluated and compared in 10 hypogonadal males and 10 normal, age-matched controls. In 6 of the subjects an investigation was also carried out into the effects of testosterone administration on lumbar BMC, calcitonin (CT) response to hypercalcaemia, osteocalcin (BGP) and the fasting urinary calcium/creatinine and hydroxyproline/creatinine ratios. Our results confirm that male hypogonadism is characterized by a low BMC and that testosterone administration is able to improve this parameter and to increase both basal BGP and CT response to hypercalcaemia. Testosterone therefore probably acts on bone tissue through both a direct action on osteoblast cells and an improvement in CT secretion. 相似文献
4.
Alberto Falchetti Marco Di Stefano Francesca Marini Francesca Del Monte Carmelo Mavilia Debora Strigoli Maria L De Feo Giovan Isaia Laura Masi Antonietta Amedei Federica Cioppi Valentina Ghinoi Susanna Maddali Bongi Giuseppina Di Fede Carmela Sferrazza Giovan B Rini Daniela Melchiorre Marco Matucci-Cerinic Maria L Brandi 《Journal of bone and mineral research》2004,19(6):1013-1017
PDB is genetically heterogeneous. Mutations of the sequestosome1 gene have been reported in sporadic and familial forms of Paget's in patients of French Canadian and British descent. Mutational analyses in different ethnic groups are needed to accurately investigate hereditary diseases. We describe two novel mutations of sequestosome1 in 62 Italian sporadic patients, confirming the role of the encoded protein in this disorder. INTRODUCTION: Paget's disease of bone (PDB) is a relatively common disease of bone metabolism reported to affect up to 3% of whites over 55 years of age. The disorder is genetically heterogeneous, and at present, there is scientific evidence that at least eight different human chromosomal loci are correlated with its pathogenesis. Mutations of the sequestosome1 (SQSTM1) gene were identified as responsible for most of the sporadic and familial forms of Paget in patients of French Canadian and British descent. Such mutations were located at exon 7 and 8 levels, encoding for the ubiquitin protein-binding domain (UBA) and representing a mutational hot spot area. MATERIALS AND METHODS: To verify the involvement of this gene in Italian subjects affected by PDB, we performed mutational analysis in 62 sporadic PDB cases. RESULTS: We described three different mutations at exon 8 level: P392L, already described in the French Canadian population and families predominantly of British descendent, and two novel mutations consisting of the amino acid substitutions M404V and G425R. No significant differences in the clinical history of PDB have been observed in patients with SQSTM1 mutations in respect to those without. CONCLUSIONS: Even though our findings suggest a minor involvement of the SQSTM1 gene in the pathogenesis of sporadic Italian Paget's cases, the identification of different significant mutations within the SQSTM1 gene in unrelated, but clinically similar individuals, offers extremely convincing evidence for a causal relationship between this gene and PDB. Longitudinal studies are needed to assess the penetrance of genotype/phenotype correlations. Our findings confirm the evidence of a clustered mutation area at this level in this disorder. 相似文献
5.
Yang GC; Croaker D; Zhang AL; Manglick P; Cartmill T; Cass D 《Human molecular genetics》1998,7(6):1047-1052
Lethal white foal syndrome (LWFS) is a congenital anomaly of horses
characterized by a white coat colour and aganglionosis of the bowel, which
is similar to Hirschsprung disease (HSCR). We decided to investigate
possible mutations of the endothelin-B receptor gene ( EDNRB ) in LWFS as
recent studies in mutant rodents and some patients have demonstrated EDNRB
defects. First, we identified a full-length cDNA for horse EDNRB . This
cDNA fragment contained a 1329 bp open reading frame which encoded 443
amino acid residues. The predicted amino acid sequence was 89, 91 and 85%
identical to human, bovine and mouse as well as rat EDNRB respectively, but
only 55% identical to the human, bovine and rat endothelin A receptor
(EDNRA). Secondly, sequence analysis, together with allele-specific PCR and
the amplification- created restriction site (ACRS) technique, revealed a
dinucleotide TC-- >AG mutation, which changed isoleucine to lysine in
the predicted first transmembrane domain of the EDNRB protein. This was
associated with LWFS when homozygous and with the overo phenotype when
heterozygous.
相似文献
6.
Relationship between HLA-DRB1 and DQ alleles and the genetic susceptibility to type 1 diabetes 总被引:6,自引:0,他引:6
Objective To study the relationship between human leukocyte antigen (HLA)-DRB1 and DQ alleles and the genetic susceptibility of type 1 diabetes in North Chinese children. Methods Polymerase chain reaction (PCR) techniques were used to amplify the second exon of DRB1 and DQ alleles, after which sequence specific olignucleotide probe (SSOP) dot blot hybridization techniques were used to analyze the amplified products. Results DRB1*0301, DQA1*0301, DQB1*0201 alleles and DRB1*0301-DQA1*0501-DQB1*0201 haplotype were significantly increased in patients, while DQA1*0103 and DQB1*0601 alleles were significantly increased in controls. The distribution of DR4 and DR9 haplotypes in patients and controls were not significantly different, but DR3/DR4 and DR4/DR9 heterozygotes were significantly increased in patients. Conclusions DRB1*0301, DQA1*0301 and DQB1*0201 confer susceptibility while DQA1*0103 and DQB1*0601 confer protection to type 1 diabetes. DRB1*0301-DQA1*0501-DQB1*0201 haplotype offers a predisposition to type 1 diabetes in North Chinese. Although the distribution of DR4 and DR9 in patients and controls had no significant difference, DR3/DR4 and DR3/DR9 heterozygotes were significantly increased in patients, showing that the susceptive effects of DR3 and DR4 or DR4 and DR9 haplotypes could be added up. 相似文献
7.
We report our clinical experience with phototherapy in 3802 infants; 3629 were exposed to "standard" daylight phototherapy and 173 to "high-intensity" blue-light phototherapy. High-intensity blue-light phototherapy was twice as effective as standard daylight phototherapy in decreasing bilirubin concentrations. No failures occurred with high-intensity phototherapy compared with an overall failure rate of 1.84/1000 with daylight lamps; these cases were transferred to high-intensity phototherapy with prompt response. Rebound after cessation of phototherapy was greater in those exposed to high-intensity blue light with a significantly greater number requiring a second exposure. However, the incidence was still low. No third exposure was required in any infant. Nursing of infants under high-intensity blue light was more difficult and inconvenient as was clinical monitoring. The light also caused more stress on the nursing and medical personnel. However, the infants tolerated both types of phototherapy equally well. High-intensity blue-light phototherapy would seem to be the treatment of choice for infants with rapidly increasing or very high bilirubin levels, as well as in those not responding adequately to daylight phototherapy. 相似文献
8.
Informed consent, parental awareness, and reasons for participating in a randomised controlled study
M van Stuijvenberg MH Suur S de Vos GC Tjiang EW Steyerberg G Derksen-Lubsen HA Moll 《Archives of disease in childhood》1998,79(2):120-125
BACKGROUND: The informed consent procedure plays a central role in randomised controlled trials but has only been explored in a few studies on children. AIM: To assess the quality of the informed consent process in a paediatric setting. METHODS: A questionnaire was sent to parents who volunteered their child (230 children) for a randomised, double blind, placebo controlled trial of ibuprofen syrup to prevent recurrent febrile seizures. RESULTS: 181 (79%) parents responded. On average, 73% of parents were aware of the major study characteristics. A few had difficulty understanding the information provided. Major factors in parents granting approval were the contribution to clinical science (51%) and benefit to the child (32%). Sociodemographic status did not influence initial participation but west European origin of the father was associated with willingness to participate in future trials. 89% of participants felt positive about the informed consent procedure; however, 25% stated that they felt obliged to participate. Although their reasons for granting approval and their evaluation of the informed consent procedure did not differ, relatively more were hesitant about participating in future. Parents appreciated the investigator being on call 24 hours a day (38%) and the extra medical care and information provided (37%) as advantages of participation. Disadvantages were mainly the time consuming aspects and the work involved (23%). CONCLUSIONS: Parents' understanding of trial characteristics might be improved by designing less difficult informed consent forms and by the investigator giving extra attention and information to non-west European parents. Adequate measures should be taken to avoid parents feeling obliged to participate, rather than giving true informed consent. 相似文献
9.
Background: Cisplatin (CDDP) and 5-fluorouracil (5-FU) represent the standard chemotherapy for advanced/recurrent head and neck squamous carcinoma (HNSC); however, the duration of response is often short, with a median survival of only five to six months.Patients and methods: Patients with HNSC were treated with vinorelbine 20 mg/m2 and methotrexate 50 mg/m2 every week and bleomycin 15 mg/m2 every two weeks. All patients were previously treated with a CDDP/5-FU regimen.Results: Forty-eight patients were evaluable for response and toxicity. After a median follow-up of 15 months, 16 patients are still alive and 32 have died. We had one complete response (2%), 12 partial responses (25%) (overall response rate 27%; 95% CI: 14%–39%), 11 stabilizations (23%) and 24 progressions (50%) of disease. Neutropenia grade 3–4 was seen in 12 patients; peripheral neurotoxicity in two patients. There were no toxic deaths.Conclusions: This regimen, administered in an outpatient setting, revealed some activity as a second-line treatment in patients with HNSC, with acceptable toxicity. 相似文献
10.
A monokine regulates colony-stimulating activity production by vascular endothelial cells 总被引:20,自引:0,他引:20
Human umbilical vein endothelial cells were cultured in supernatants of peripheral blood monocytes that had been cultured for 3 days with and without lactoferrin. Colony-stimulating activity (CSA) was measured in supernatants of the endothelial cell cultures and appropriate control cultures using normal, T-lymphocyte-depleted, phagocyte-depleted, low- density bone marrow cells in colony growth (CFU-GM) assays. Monocyte- conditioned medium contained a nondialyzable, heat labile factor that enhanced 4-15--fold the production of CSA by endothelial cells. The addition of lactoferrin to monocyte cultures reduced the activity of this monokine by 69%. Lactoferrin did not inhibit CSA production by monokine-stimulated endothelial cells. Therefore, vascular endothelial cells are potent sources of CSA, the production of CSA by these cells is regulated by a stimulatory monokine, and the production and/or release of the monokine is inhibited by lactoferrin, a neutrophil- derived putative feedback inhibitor of granulopoiesis. Inasmuch as a similar monokine is known to stimulate CSA production by fibroblasts and T lymphocytes, we suggest that mononuclear phagocytes play a pivotal role in the regulation of granulopoiesis by recruiting a variety of cell types to produce CSA. 相似文献