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181.
182.
Hong HL; Devereux TR; Melnick RL; Eldridge SR; Greenwell A; Haseman J; Boorman GA; Sills RC 《Carcinogenesis》1997,18(4):783-789
Isoprene is the 2-methyl analog of 1,3-butadiene, a genotoxic and
carcinogenic compound in rats and mice. Male B6C3F1 mice were exposed to 0,
2200 or 7000 ppm isoprene by inhalation (6 h/day; 5 days/week) for 26
weeks. Following a 26-week recovery period, an increased incidence of
Harderian gland (HG) neoplasms was observed at both concentrations. The
present study was designed to characterize genetic alterations in the K-ras
and H-ras protooncogenes in HG neoplasms. Mutations in K-ras and H-ras were
identified by single-strand conformational analysis and direct sequencing
of polymerase chain reaction (PCR) amplified DNA, isolated from
paraffin-embedded sections of HG neoplasms. A higher frequency of ras
mutations, in particular K- ras mutations, was detected in isoprene-induced
neoplasms than in 1,3- butadiene-induced or control HG neoplasms. All of
the isoprene-induced HG neoplasms exhibited activated K-ras (60%) or H-ras
(40%) mutations. In contrast, ras mutations were detected in 69% of HG
neoplasms from 1,3-butadiene exposed mice (14% K-ras and 55% H-ras) and in
56% of HG neoplasms obtained from control B6C3F1 mice (8% K-ras and 48%
H-ras). The predominant mutations in isoprene-induced HG neoplasms, but not
in previously or newly analysed 1,3-butadiene-induced HG neoplasms,
consisted of A-->T transversions (CAA-->CTA) at K-ras codon 61
(15/30) and C-->A transversions (CAA-->AAA) at H-ras codon 61 (8/30).
Two- thirds of the K-ras CTA mutations were detected in HG neoplasms from
the 2200 ppm exposure group while one-third was present in the 7000 ppm
group. Isoprene-induced HG neoplasms with K-ras or H-ras mutations had an
elevated proliferating cell nuclear antigen (PCNA) index, compared to
spontaneous HG neoplasms without ras mutations. The high frequency and
specificity of the ras mutation profile suggest that ras protooncogene
activation contributes to isoprene-induced HG tumorigenesis.
相似文献
183.
The organoselenium compounds benzyl selenocyanate (BSC) and 1,4-
phenylenebis(methylene)selenocyanate (p-XSC), as well as sodium selenite,
are effective chemopreventive agents for various chemically induced tumors
in animal models at both the initiation and postinitiation stages. The
mechanisms involved at the postinitiation stage are not clear. Because
several lines of evidence indicate that inhibition of excess DNA
(cytosine-5)-methyltransferase (Mtase) may be a sufficient factor for the
suppression or reversion of carcinogenesis, we examined the effects of
sodium selenite, BSC, p-XSC and benzyl thiocyanate (BTC), the sulfur analog
of BSC, on Mtase activity in nuclear extracts of human colon carcinomas,
and of p-XSC on the Mtase activity of HCT116 human colon carcinoma cells in
culture. For this purpose, we developed an improved Mtase assay, in which
the incorporation of the methyl-[3H] group from S-adenosyl[methyl-
3H]methionine into deoxycytidine of poly(dI-dC)-poly(dI-dC), is
specifically determined by HPLC with radioflow detection after enzymatic
hydrolysis, enhancing specificity and reliability. In a variation, using
SssI methyltransferase and labeled S- adenosylmethionine, the overall
methylation status of DNA in various tissues can also be compared.
Selenite, BSC and p-XSC inhibited Mtase extracted from a human colon
carcinoma with IC50s of 3.8, 8.1 and 5.2 microM, respectively; BTC had no
effect. p-XSC also inhibited the Mtase activity and growth of human colon
carcinoma HCT116 cells, with an IC50 of approximately 20 microM. The
improved Mtase assay should prove to be a reliable method for screening
potential Mtase inhibitors, especially using cells in culture. We suggest
that inhibition of Mtase may be a major mechanism of chemoprevention by
selenium compounds at the postinitiation stage of carcinogenesis.
相似文献
184.
Studies of iron deposits, inducible nitric oxide synthase and nitrotyrosine in a rat model for esophageal adenocarcinoma 总被引:6,自引:7,他引:6
A rat model was developed recently in our laboratory to study the
pathogenesis of Barrett's esophagus (BE) and its progression to esophageal
adenocarcinoma (EAC). Eight-week-old male Sprague-Dawley rats underwent
esophagoduodenal anastomosis (EDA) to produce gastric and duodenal reflux
in their distal esophagi. The rats were given iron dextran (50 mg of Fe/kg,
i.p.) starting 2 weeks after surgery and this was continued once a month.
BE was observed as early as week 3 and the incidence of BE and EAC
increased with time: 58 and 17% at week 23; 91 and 73% at week 31. There
was a progression in epithelial cell proliferation and inflammation from
mild to severe in the distal one- third of the esophagus. Iron deposition
in the esophagus also increased with time. Iron deposits in the stromal
tissue adjacent to the epithelium in the distal one-third of the esophagus
were associated with areas of severe inflammation. Immunohistochemical
analysis showed positive inducible nitric oxide synthase (iNOS) expression
in the stromal macrophages directly beneath the epithelium in the distal
one- third of the esophagus in 36, 83 and 100% of the rats at weeks 17, 23
and 31, respectively. A significant increasing linear trend (P=0.001) was
seen in nitrotyrosine immunostaining (number of positive cells/high power
field) in the distal esophagus. Strong positive nitrotyrosine staining was
seen in the macrophages and weaker positive staining was seen in the
adjacent epithelium starting at week 17. Furthermore, iron supplemented
rats killed at week 31 had significantly higher (P < 0.05) levels of
inflammation, cell proliferation, iNOS and nitrotyrosine as well as more
tumors in their distal esophagi than did rats that received no iron
supplement. These results suggest that iron supplementation enhanced
inflammation and the production of reactive oxygen and nitrogen species in
the esophageal epithelium. These processes could contribute to the
formation of BE and its progression to EAC.
相似文献
185.
Embryo transfer--can we learn anything new from the observation of junctional zone contractions? 总被引:2,自引:6,他引:2
Lesny P; Killick SR; Tetlow RL; Robinson J; Maguiness SD 《Human reproduction (Oxford, England)》1998,13(6):1540-1546
To assess whether embryo transfer can alter junctional zone contractility,
we studied the effect of easy and difficult mock transfers in 14 oocyte
donors during in-vitro fertilization (IVF) cycles. An Echovist bolus (30
microl) was used to represent embryos and transfer medium. An 'easy'
transfer was judged to be an atraumatic insertion of the catheter without
touching the uterine fundus. A 'difficult' embryo transfer was mimicked by
deliberately touching the uterine fundus twice with the soft end of the
cannula. Transvaginal scan images were recorded, digitized and converted
into five times normal speed to allow us to evaluate junctional zone
contractility. Easy mock embryo transfers did not change endometrial
mechanical activity. Echovist remained in the upper part of the uterine
cavity and was not dispersed after 45 min. A difficult procedure generated
strong random waves in the fundal area and waves from fundus to cervix
which relocated the Echovist in six out of seven cases. We observed
movements of the transfer bolus from the upper part of the uterus towards
the cervix (four cases) and into Fallopian tubes (two patients). Our study
confirms that the mechanical activity of the uterus is capable of
relocating intrauterine embryos and that this activity depends on physical
stimulation. Junctional zone contractions can be implicated in cases of
IVF/embryo transfer failure or ectopic gestation.
相似文献
186.
Kim YC, Kim SR, Markelonis GJ, Oh TH (1998): Ginsenosides Rb1 and Rg3 protect cultured rat cortical cells from glutamate-induced neurodegeneration. J Neurosci Res 53:426–432. On page 427 of the article referenced above, under the heading Assessment of Neurotoxicity in the Materials and Methods section, the formula given for the assessment of percentage cell viability was printed incorrectly. The formula is correctly stated in a footnote to Table 1 on page 429. The correct formula appears below: 100 × (OD of glutamate + ginsenoside-treated – OD of glutamate-treated)/(OD of control – OD of glutamate-treated). The publisher regrets this error. 相似文献
187.
188.
Bowen AR Vester A Marsden L Florell SR Sharp H Summers P 《American journal of obstetrics and gynecology》2008,199(5):467-467.e6
Sixty-one percent of refractory vulvodynia patients evaluated in a tertiary care vulvovaginal clinic had clinically relevant dermatoses based on dermatopathologist-analyzed vulvar biopsy including: lichen sclerosus, allergic/irritant dermatitis, lichen planus, and other inflammatory or neoplastic dermatoses. Given the frequency of dermatologic disease, vulvar biopsy and analysis by a dermatopathologist are recommended in patients with vulvodynia. 相似文献
189.
目的:分析体表高频超声检测家兔血管内球囊成形术后再狭窄程度与组织病理学分析的相关性。评估体表超声检测的可行性、可靠性及应用价值。方法:实验于2002-03/2003-12在北京中医药大学中医内科学重点学科实验室完成。①日本大耳白兔26只,随机分为正常组10只、假手术组6只、模型组10只。②模型组电刺激兔颈总动脉,电流1.2mA,刺激12~15min,术后第2天喂饲高脂饲料共8周,假手术组仅剥离颈总动脉,不做电刺激,喂高脂饲料,正常组不施加任何干预因素。③模型组和假手术组根据B超选择颈总动脉有斑块或血流明显改变者行球囊血管内成形术。分别于电刺激后8周、血管成形术后4周行超声检查动脉内径和动脉内膜厚度。④所有动物于血管成形术后4周处死取材,进行病理学半定量分析,并与超声测量结果进行相关分析。结果:进入结果分析数量24只,正常组中途死亡1只,原因为牙齿畸型影响进食。模型组1只因电刺激8周时超声评价颈动脉未形成斑块及血流无明显改变而剔出实验。①超声检测电刺激8周时正常组内膜厚为(0.028±0.004)cm,模型组管壁明显增厚(0.043±0.014)cm,差异有显著性(P<0.05),至血管成形术后膜厚增加更明显(0.064±0.002)cm,内径稍有扩大,但差异不显著。②超声检测模型组颈动脉内径与膜厚的测量结果与病理学测量结果呈正相关关系(OR=0.361,P<0.05;OR=0.526,P<0.01),病理狭窄率与超声是否检测到斑块呈正相关关系(OR=0.796,P<0.01)。结论:体表高频超声在评价家兔颈动脉狭窄诊断中有一定应用价值,与病理学半定量分析结果相关性良好。 相似文献
190.