全文获取类型
收费全文 | 253篇 |
免费 | 23篇 |
国内免费 | 27篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 19篇 |
妇产科学 | 3篇 |
基础医学 | 30篇 |
口腔科学 | 18篇 |
临床医学 | 59篇 |
内科学 | 59篇 |
皮肤病学 | 8篇 |
神经病学 | 3篇 |
特种医学 | 25篇 |
外科学 | 21篇 |
综合类 | 18篇 |
预防医学 | 7篇 |
眼科学 | 1篇 |
药学 | 15篇 |
中国医学 | 1篇 |
肿瘤学 | 15篇 |
出版年
2023年 | 2篇 |
2022年 | 2篇 |
2021年 | 2篇 |
2020年 | 1篇 |
2019年 | 6篇 |
2018年 | 5篇 |
2017年 | 6篇 |
2016年 | 8篇 |
2015年 | 7篇 |
2014年 | 6篇 |
2013年 | 13篇 |
2012年 | 6篇 |
2011年 | 3篇 |
2010年 | 11篇 |
2009年 | 11篇 |
2008年 | 5篇 |
2007年 | 12篇 |
2006年 | 5篇 |
2005年 | 13篇 |
2004年 | 4篇 |
2003年 | 1篇 |
2002年 | 7篇 |
2001年 | 9篇 |
2000年 | 4篇 |
1999年 | 9篇 |
1998年 | 21篇 |
1997年 | 18篇 |
1996年 | 17篇 |
1995年 | 13篇 |
1994年 | 14篇 |
1993年 | 3篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1990年 | 3篇 |
1989年 | 7篇 |
1988年 | 5篇 |
1987年 | 5篇 |
1986年 | 10篇 |
1985年 | 4篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1978年 | 3篇 |
1977年 | 3篇 |
1976年 | 4篇 |
1975年 | 3篇 |
1967年 | 1篇 |
排序方式: 共有303条查询结果,搜索用时 187 毫秒
81.
Establishment of two new myeloma cell lines from bilateral pleural effusions: evidence for sequential in vivo clonal change 总被引:3,自引:0,他引:3
Durie BG; Vela E; Baum V; Leibovitz A; Payne CM; Richter LC; Grogan TM; Trent JM 《Blood》1985,66(3):548-555
Two new human myeloma cell lines have been established from a 36-year- old woman with refractory IgG kappa multiple myeloma in whom bilateral malignant pleural effusions developed. The malignant plasma cells from each effusion were set up in a liquid culture using an L-15 medium containing catalase, glutathione, selenous acid, ascorbic acid, insulin, transferrin, additional glutamine hydrocortisone, and 2- mercaptoethanol and designated as M-3 medium. Two IgG kappa cell lines, LB -831 and LB-832, were established and proved to be Epstein-Barr virus negative using the internal repeat sequence DNA probe. Characteristic plasma cell morphology was evident by light and electron microscopy. Immunotyping revealed an IgG kappa , B1+, B2-, Ia (HLA- DR)+, CALLA+ phenotype for each cell line as well as for the original pleural fluid and bone marrow myeloma cells. The supernatants also contained IgG kappa, beta 2 microglobulin, and large amounts of osteoclast-activating factor (indicating bone-resorbing activity). Cytogenetic analysis of the LB-831 cell line revealed a nearly triploid highly abnormal karyotype with numerous clonal chromosomal abnormalities involving chromosomes 1, 3, 5, 7, 13, and 15; several structurally abnormal marker chromosomes; and a putative homogeneously staining region on chromosome 7p at band p22. Analysis of the LB-832 cell line revealed several additional clonal abnormalities. These additional cytogenetic changes suggest that in vivo sequential clonal evolution occurred in this patient. Therefore, two new but related cell lines have been established, which should prove useful for further biological studies. 相似文献
82.
83.
RL HENRY LC HETTIARACHCHI P COLLEY C COLLLINS EV O'LOUGHLIN DM COOPER 《Journal of paediatrics and child health》1996,32(5):416-418
Objective : To determine the genotype of patients attending the cystic fibrosis clinic at John Hunter Hospital, Newcastle, Australia.
Methodology : Seventy-five of the 76 patients attending the clinic over a 6 month period had blood collected for genetic analysis of 17 of the cystic fibrosis (CF) gene mutations.
Results : Sixty-one per cent of the patients were homozygous for the ΔF508 mutation and all except one child had at least one ΔF508 mutation.
Discussion : Nearly 80% of the CF genes were the ΔF508 mutation. This prevalence suggests that the obligatory false negative rate of a newborn screening programme for CF based on a combination of immunoreactive trypsin and the ΔF508 gene may be as low as 4-5%. 相似文献
Methodology : Seventy-five of the 76 patients attending the clinic over a 6 month period had blood collected for genetic analysis of 17 of the cystic fibrosis (CF) gene mutations.
Results : Sixty-one per cent of the patients were homozygous for the ΔF508 mutation and all except one child had at least one ΔF508 mutation.
Discussion : Nearly 80% of the CF genes were the ΔF508 mutation. This prevalence suggests that the obligatory false negative rate of a newborn screening programme for CF based on a combination of immunoreactive trypsin and the ΔF508 gene may be as low as 4-5%. 相似文献
84.
85.
86.
Morlet N Stayt J Vaegan Salonikas C Naidoo D Crouch R Graham G Coroneo M 《Australian and New Zealand journal of ophthalmology》1999,27(5):342-349
BACKGROUND: Although Cytomegalovirus (CMV) retinitis is now a common intraocular infection, current therapy is only virostatic so ongoing treatment is required. Etoposide was found to be virocidal for CMV in laboratory experiments and it might prove to be beneficial clinically. We investigated the toxicity and intraocular concentration of etoposide (VP16) and its new analogue etoposide-phosphate (VP16P) following intravitreal injections in rabbit eyes. METHODS: First a sequential dose-response was assessed with flash electroretinogram for both eyes of light- and dark-adapted rabbits (n = 7; one rabbit for each dose) over a range of light intensities before and after intravitreal injection of VP16 or VP16P to one eye; the other eye was injected with normal saline as a control. A multidose study was then performed on four rabbits. A non-toxic dose of VP16P (50 or 75 g) was injected into the vitreous of one eye on four occasions 1 week apart. A photopic electroretinogram was performed before the first injection and 6 weeks after the last injection. All the eyes from the electroretinogram studies were fixed in formalin, placed in paraffin, then stained with haematoxylin and eosin and examined under a light microscope. To determine the time-course of the intraocular concentrations of VP16P a sequential pharmacokinetic study was performed using a further 12 rabbits. Each rabbit was injected with 50 g VP16P to one eye and 75 g VP16P to the other eye. Three of these rabbits were killed at 1, 3, 6 and 9 h after injection. Samples of vitreous were assayed for both VP16 and VP16P using HPLC. An in vitro dose response assay was performed using third-passage bovine retinal pigment epithelial (RPE) cells cultured in Dulbecco's modified Eagles medium with fetal calf serum. The effect of a log-dose increment of VP16P on the RPE cell proliferation was assessed using tritiated thymidine incorporation. RESULTS: The electroretinogram studies suggested that VP16 was toxic even with the 10 g dose. For VP16P a toxic effect was noted following injection of a single dose greater than 100 g. Multiple injections of 50 or 75 g VP16P did not produce a toxic response. Histological examination demonstrated significant abnormality only with the 500 g dose of VP16 or VP16P. VP16P was rapidly metabolized to VP16 in the eye, producing concentrations of 2.0 g/mL or more for up to 9 h following a 75-microg dose. This suggests that the electroretinogram findings following VP16 injections were confounded by a toxic effect of the ethanol solvent (which is absent from the VP16P preparation). VP16P was quite potent, the ID50 was about 0.1 g/mL for bovine RPE cells in the in vitro assay. DISCUSSION: These results indicate that multiple 75-gVP16P intravitreal injections were not toxic to the rabbit eye and provide a therapeutic intraocular concentration for up to 9 h after the injection. 相似文献
87.
Roessler E; Belloni E; Gaudenz K; Vargas F; Scherer SW; Tsui LC; Muenke M 《Human molecular genetics》1997,6(11):1847-1853
Holoprosencephaly (HPE) is the most common brain anomaly in humans,
involving abnormal formation and septation of the developing central
nervous system. Among the heterogeneous causes of HPE, mutations in the
Sonic Hedgehog (SHH) gene have been shown to result in an autosomal
dominant form of the disorder. Here we describe a total of five different
mutations in the processing domain encoded by exon 3 of SHH in familial and
sporadic HPE. This is the first instance in humans where SHH mutations in
the domain responsible for autocatalytic cleavage and cholesterol
modification of the N-terminal signaling domain of the protein have been
observed.
相似文献
88.
89.
Layman LC; Edwards JL; Osborne WE; Peak DB; Gallup DG; Tho SP; Reindollar RH; Roach DJ; McDonough PG; Lanclos KD 《Molecular human reproduction》1997,3(4):315-320
Women with recurrent abortion, primary unexplained infertility, and
gestational trophoblastic neoplasia (GTN) manifest disordered human
chorionic gonadotrophin (HCG) secretion. Mutations in the HCG
beta/luteinizing hormone (LH) beta gene complex could cause aberrant HCG
production in these disorders. The purpose of this study was to determine
whether HCG beta gene deletions occur in women with recurrent abortion or
primary unexplained infertility, and whether HCG beta gene duplications are
present in women with GTN. DNA was extracted from 10 patients with
unexplained recurrent abortion, 10 patients with unexplained primary
infertility, 12 patients with GTN, three partners of women with GTN, and 30
controls. Southern blots were constructed and hybridized with DNA probes
for HCG beta-5 and the LH beta gene. No gene deletions were identified in
patients with recurrent abortion or primary unexplained infertility.
Likewise, no gene duplications were identified in women with GTN. A
previously described Mbol restriction fragment length polymorphism (RFLP)
was identified in both patients and controls. A new Pstl RFLP was also
characterized, but was present in patients and controls.
Deletion/duplication mutations in the HCG beta/LH beta gene complex do not
appear to be common causes of aberrant HCG production in humans with these
disorders.
相似文献
90.