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11.
Alternative splicing of exon 14 determines nuclear or cytoplasmic localisation of fmr1 protein isoforms 总被引:6,自引:9,他引:6
Impaired expression of the FMR1 gene is responsible for the fragile X
mental retardation syndrome. The FMR1 gene encodes a cytoplasmic protein
with RNA-binding properties. Its complex alternative splicing leads to
several isoforms, whose abundance and specific functions in the cell are
not known. We have cloned in expression vectors, cDNAs corresponding to
several isoforms. Western blot comparison of the pattern of endogenous FMR1
proteins with these transfected isoforms allowed the tentative
identification of the major endogenous isoform as ISO 7 and of a minor band
as an isoform lacking exon 14 sequences (ISO 6 or ISO 12), while some other
isoforms (ISO 4, ISO 5) were not expressed at detectable levels.
Surprisingly, in immunofluorescence studies, the transfected splice
variants that exclude exon 14 sequences (and have alternate C-terminal
regions) were shown to be nuclear. Such differential localisation was
however not seen in subcellular fractionation studies. Analysis of various
deletion mutants suggests the presence of a cytoplasmic retention domain
encoded in exon 14 and of a nuclear association domain encoded within the
first eight exons that appear however to lack a typical nuclear
localisation signal.
相似文献
12.
0 引言 胰腺多房性潴留性囊肿极为罕见,我科收治1例,报道如下.1 病例报告 患者,男,29岁,因发现右上腹包块11d入院,缘于11d前无明显诱因感右上腹痛,仅局限于右上腹部,无肩背部放散痛,伴间歇性发热,体温最高达38.3℃,经抗炎,对症治疗无效.并逐渐可触及右上腹有一肿块,在当地医院行穿刺检查为脓血性液体.镜检发现炎性细胞,B超示:胆囊窝下方及右肾内侧及腹腔动脉,下腔静脉外前方可见异常区,大小约9.1cm×6.6cm×7.6cm,边界清楚,形态不规则,内呈蜂窝状,可见多个大小不等的液性暗区,CT示:右上腹部上腔静脉前方6.0cm×9.0cm肿块和周围组织粘… 相似文献
13.
A young boy presented with an uncommon finding of impaction of upper right central incisor and transposition of canine and lateral incisor on the same side. Esthetic management of his cosmetic problem which included fixed appliance therapy followed by light cure restorations is discussed.KEY WORDS: Impaction, Transposition 相似文献
14.
15.
Isolation and characterization of propagable cell lines (HUNC) from the androgen-sensitive Dunning R3327H rat prostatic adenocarcinoma 总被引:1,自引:0,他引:1
Presnell SC; Borchert KM; Glover WJ; Gregory CW; Mohler JL; Smith GJ 《Carcinogenesis》1998,19(4):585-590
The Dunning H rat prostate tumor (R3327H) is a widely used experimental
model of human prostatic adenocarcinoma (CaP). The Dunning H tumor has been
characterized as androgen-sensitive, androgen-receptor (AR) positive,
prostate-specific antigen and prostatic acid phosphatase (PAP) positive. To
date, the tumor has been maintained by serial passage in vivo because of
the lack of an in vitro cell line that retains the characteristics of the
in vivo tumor. The objective of the present study was to establish a
propagable cell line from R3327H adenocarcinoma that maintained androgen
sensitivity and expression of AR, PSA and PAP. Tissue harvested from an in
vivo R3327H tumor was dissociated with collagenase and placed into
Richter's improved media (with supplements). A cytokeratin-positive
epithelial cell line (HUNC- E) and a vimentin-positive stromal cell line
(HUNC-S) were generated from the primary culture, subcultured continuously
for >300 days, and passaged >50 times. Survival of the HUNC-E cell
line in vitro depended on several media supplements, including
nicotinamide, insulin, transferrin, selenium and epidermal growth factor
(EGF). HUNC-E cells expressed AR and produced PSA and PAP throughout the
culture period, as confirmed by immunocytochemistry and Western blot
analyses. Addition of 14 nM testosterone (T) or dihydrotestosterone (DHT)
to HUNC-E cells, stimulated DNA synthesis as well as anchorage-independent
growth and PSA production, which demonstrated the androgen-sensitive nature
of the cells in vitro. When HUNC-E and HUNC-S cells were combined in a 3:1
ratio and introduced subcutaneously into syngeneic male hosts, tumors
formed in 2/3 animals with an average latency of 7 months. RT-PCR and
immunocytochemical characterization of the HUNC cell lines revealed that
the cells expressed several growth factors and their cognate receptors,
including HGF, TGF-alpha and the TGF-betas, indicating the establishment of
potential autocrine loops in the neoplastic cells. The HUNC-E and HUNC-S
CaP cell lines, which retain the characteristics of the epithelial and
stromal components of the in vivo R3327H tumor, will allow a more thorough
and informative molecular and biological analysis of prostatic
adenocarcinoma.
相似文献
16.
Previous work has shown that sustained increased and decreased cell
proliferation, induced by dietary zinc deficiency and caloric restriction
respectively, influence the course of N- nitrosomethylbenzylamine
(NMBA)-induced esophageal carcinogenesis in rats. The present study
considered whether the increased cell proliferation and esophageal tumor
incidence induced by zinc deficiency are reversed upon zinc replenishment.
Weanling rats were maintained initially on a deficient diet containing 4
p.p.m. zinc. After 5 weeks, carcinogen-treated animals were given six
intragastric doses of NMBA (2 mg/kg twice weekly). Controls were untreated.
After the second NMBA dose, the rats were divided into three dietary
groups. One group was continued on the deficient diet, while the other two
groups were switched to diets containing either 75 or 200 p.p.m. zinc, with
half of the members in each group fed ad libitum and half pair-fed with
deficient rats. NMBA-untreated controls were similarly replenished. At
various time points, esophageal cell proliferation was assessed in five
animals from each group by immunohistochemical detection of cells in S
phase, with in vivo 5-bromo-2'deoxyuridine labeling. At 11 weeks after the
first dose, esophageal tumor incidence was greatly reduced, from 100% in
the deficient group to 26 and 14% respectively in the replenished groups
fed ad libitum 75 and 200 p.p.m. zinc and to 14 and 11% respectively in the
replenished groups pair-fed 75 and 200 p.p.m. zinc. In addition, the number
of tumors per esophagus was reduced from 9.93 +/- 4.25 in deficient rats,
to a range of 0.11 +/- 0.31-0.30 +/- 0.54 in replenished animals. Following
zinc replenishment, esophageal cell proliferation, as measured by labeling
index (LI), the number of labeled cells and the total number of cells, was
markedly decreased in NMBA-untreated and -treated esophagi as compared with
those in corresponding deficient esophagi. Thus, the esophageal cell
proliferation induced by zinc deficiency is reversed by zinc replenishment
and replenished animals have a markedly lower incidence of esophageal
tumors.
相似文献
17.
液基细胞学结合阴道镜检查在北京市社区妇女宫颈病变筛查中的意义 总被引:2,自引:0,他引:2
目的探讨宫颈液基细胞学及阴道镜检查在北京市社区妇女宫颈病变筛查中的临床意义。方法2006年6月至2007年6月对北京市展览路社区的795位20~54岁有性生活的妇女进行筛查。筛查对象接受妇科检查时,留取宫颈超柏氏薄层液基细胞学检测标本,并对宫颈细胞学异常者行阴道镜检查及活组织检查。结果宫颈细胞学阳性[≥ASC-US(不能明确意义的不典型鳞状细胞)]45例,占5.7%(45/795)。其中ASC-US33例,占73.3%(33/45);低度鳞状上皮内病变8例;高度鳞状上皮内病变3例;不典型腺细胞1例。细胞学阴性750例,占94.3%(750/795)。宫颈细胞学阳性的45例中,5例拒绝行阴道镜检查,占11.1%(5/45)。在行阴道镜活组织病理检查的40例中,慢性宫颈炎11例(27.5%);宫颈湿疣14例(35.0%);宫颈上皮内瘤样病变(CIN)1为7例(17.5%);CIN2为3例(7.5%);CIN3为4例(10.0%);早期浸润癌1例(2.5%)。细胞学阴性的750例中,宫颈湿疣2例(0.3%);CIN1为5例(0.7%);宫颈低级别腺上皮内病变1例(0.1%)。宫颈液基细胞学筛查CIN1及以上宫颈病变和宫颈癌的敏感度71.4%,特异度94.2%,阳性预测值37.5%,阴性预测值99.2%;筛查CIN2及以上宫颈病变和宫颈癌的敏感度100.0%,特异度96.0%,阳性预测值20.5%,阴性预测值100.0%。结论应重视并及时进行北京市社区人群宫颈病变的早期筛查,薄层液基细胞学结合阴道镜活组织检查及病理学检查,对提高早期宫颈癌筛查的准确性效果明显。 相似文献
18.
19.
20.
Solary E; Witz B; Caillot D; Moreau P; Desablens B; Cahn JY; Sadoun A; Pignon B; Berthou C; Maloisel F; Guyotat D; Casassus P; Ifrah N; Lamy Y; Audhuy B; Colombat P; Harousseau JL 《Blood》1996,88(4):1198-1205
A phase III prospective randomized multicenter study was performed to determine whether quinine could improve the response rate of poor-risk acute leukemias (ALs) to standard chemotherapy including a multidrug resistance (MDR)-related cytotoxic agent. The rationale of the study was based on the negative prognostic value of MDR phenotype in ALs and the ability of quinine to reverse this phenotype both in vitro and ex vivo. Three hundred fifteen patients (median age, 49 years; range, 16 to 65) with relapsed (n = 108) or refractory (n = 32) acute myeloblastic leukemia (AML), relapsed (n = 27) or refractory (n = 9) acute lymphoblastic leukemia (ALL), secondary AL (n = 22) or blastic transformation of myelodysplastic syndrome ([MDS] n = 74) or myeloproliferative syndrome ([MPS] n = 43) were randomly assigned to receive mitoxantrone ([MXN] 12 mg/m2/d, days 2 to 5) and cytarabine ([Ara-C] 1 g/m2/12 h, days 1 to 5) alone or in combination with quinine (30 mg/kg/d, days 1 to 5; continuous intravenous infusion beginning 24 hours before MXN infusion). Side effects of quinine were observed in 56 of 161 quinine-treated patients and disappeared in all but four cases after one or two 20% dose decreases. Sera from quinine-treated patients showed increased MXN uptake in an MDR-positive cell line compared with matched sera obtained before quinine infusion. Quinine induced a significant increase in the incidence of nausea, vomiting, mucositis, and cardiac toxicity. A complete response (CR) was observed in 85 of 161 patients (52.8%) from the quinine-treated group versus 70 of 154 patients (45.5%) in the control group (P = .19). The most important differences between quinine and control group CR rates were observed in patients with refractory AMLs and blastic transformation of MDS and MPS. The CR rate was higher in P-glycoprotein-positive cases, although the difference was not significant. Failure of the regimen due to blastic persistence or blast number increase was higher in the control group (61 of 154 patients) than in the quinine group (45 of 161, P = .04). Early death was observed in eight cases (four in each arm) and death in aplasia in 27 cases (20 in quinine group v seven in control group, P = .01). The significant increase of toxicity in the quinine arm could have masked the clinical benefit of MDR reversion in poor- risk ALs. 相似文献