全文获取类型
收费全文 | 3263篇 |
免费 | 233篇 |
国内免费 | 6篇 |
专业分类
耳鼻咽喉 | 116篇 |
儿科学 | 114篇 |
妇产科学 | 97篇 |
基础医学 | 416篇 |
口腔科学 | 120篇 |
临床医学 | 378篇 |
内科学 | 441篇 |
皮肤病学 | 82篇 |
神经病学 | 269篇 |
特种医学 | 228篇 |
外科学 | 270篇 |
综合类 | 73篇 |
一般理论 | 1篇 |
预防医学 | 205篇 |
眼科学 | 106篇 |
药学 | 211篇 |
1篇 | |
肿瘤学 | 374篇 |
出版年
2021年 | 24篇 |
2019年 | 35篇 |
2018年 | 46篇 |
2017年 | 27篇 |
2016年 | 38篇 |
2015年 | 39篇 |
2014年 | 54篇 |
2013年 | 98篇 |
2012年 | 90篇 |
2011年 | 102篇 |
2010年 | 96篇 |
2009年 | 79篇 |
2008年 | 97篇 |
2007年 | 122篇 |
2006年 | 147篇 |
2005年 | 145篇 |
2004年 | 125篇 |
2003年 | 111篇 |
2002年 | 98篇 |
2001年 | 86篇 |
2000年 | 88篇 |
1999年 | 116篇 |
1998年 | 72篇 |
1997年 | 72篇 |
1996年 | 62篇 |
1995年 | 50篇 |
1994年 | 69篇 |
1993年 | 47篇 |
1992年 | 90篇 |
1991年 | 84篇 |
1990年 | 89篇 |
1989年 | 93篇 |
1988年 | 75篇 |
1987年 | 75篇 |
1986年 | 59篇 |
1985年 | 52篇 |
1984年 | 62篇 |
1983年 | 62篇 |
1982年 | 43篇 |
1981年 | 35篇 |
1980年 | 32篇 |
1979年 | 54篇 |
1978年 | 41篇 |
1977年 | 26篇 |
1976年 | 28篇 |
1975年 | 22篇 |
1974年 | 36篇 |
1973年 | 21篇 |
1971年 | 17篇 |
1970年 | 21篇 |
排序方式: 共有3502条查询结果,搜索用时 31 毫秒
61.
J. Graham Sharp James W. Osborne Ph.D. H. F. Cheng K. L. Coop George R. Zimmerman 《European journal of nuclear medicine and molecular imaging》1982,7(1):28-34
Radioiodinated antitumor (Ab-gamma globulins), non-tumor-specific Ab, and R131ISA were used for imaging radiation-induced intestinal tumors in rats. Each agent detected tumors larger than 2 g, but labeled Ab were most efficient in detecting smaller tumors. Tissue distribution studies showed that while purified Ab localized specifically in tumors, unpurified Ab concentrated in the tumor by a mechanism not considered immunological. Localization was variable and the concentration of antitumor Ab reached useful levels only in a small number of cases. The use of high specific activity purified Ab unexpectedly decreased the concentrations of label observed in the tumors when compared with the use of the same activity of low specific activity purified Ab. These results indicated the presence of circulating tumor antigens which were capable of binding the injected Ab. Subsequently, these findings have been substantiated. Thus the animal-to-animal variability could be explained on the basis of differing degrees of interaction of injected Ab with circulating tumor antigens. The usefulness of labeled purified or monospecific antitumor antibodies for tumor imaging and therapy would thus be influenced by the extent of such interactions.This work was presented in part at the Twentieth Annual Meeting of the Radiation Research Society, Portland, Oregon, May, 1972. 相似文献
62.
Grazia Arpino Stephanie J Green D Craig Allred Dannika Lew Silvana Martino C Kent Osborne Richard M Elledge 《Clinical cancer research》2004,10(17):5670-5676
PURPOSE: Preclinical data indicate that expression of the ErbB family of receptors, such as HER-2 and HER-1 (EGFR) may be involved in endocrine resistance. Evidence of resistance from clinical studies has been inconsistent. The present study examined whether HER-2 gene amplification or HER-1 expression predicted response to tamoxifen. PATIENTS AND METHODS: Three hundred and forty nine patients had estrogen receptor (ER)-positive breast cancer and received daily tamoxifen as initial therapy for advanced disease. HER-2 gene amplification, detected by fluorescence in situ hybridization, and HER-1 expression, evaluated by immunohistochemistry, was determined on 136 and 204 patients, respectively. RESULTS: HER-2 amplification was correlated with lower ER (P = 0.02), HER-1 positivity (P = 0.004), and HER-2 protein overexpression (P < 0.00001). The response rate was 56% for HER-2 non-amplified versus 47% for HER-2 amplified tumors (P = 0.38), and 58% for HER-1-negative versus 36% for HER-1-positive (P = 0.05). Time to treatment failure (TTF) was 7 months for non-amplified HER-2 tumors and 5 months (P = 0.007) for amplified HER-2 tumors, and there was a trend toward a better overall survival (OS) in patients with non-amplified HER-2 tumors (median 31 versus 25 months, respectively, P = 0.07). For positive versus negative HER-1 tumors, TTF was 4 versus 8 months (P = 0.08) and median survival was 24 versus 31 months (P = 0.41). Combining HER-1 expression and HER-2 gene status, patients with both negative HER-1 expression and non-amplified HER-2 had longer TTF (P = 0.001) and OS (P = 0.03) than if either were positive. In multivariate analysis, HER-2 was not an independent factor for TTF and OS, although HER-1 was significant for TTF only (P = 0.001). CONCLUSION: Patients with HER-2 amplification and HER-1 expression had lower ER levels and were modestly less responsive to tamoxifen, suggesting that molecular events in addition to those involving the ErbB receptors are important in determining the endocrine-resistant phenotype. 相似文献
63.
OBJECTIVES: To study the efficacy of otoacoustic emissions (OAEs) as a screening test for hearing impairment in children with acute bacterial meningitis. Hearing tests were performed before discharge from the hospital in an attempt to improve coverage and avoid delays in the diagnosis of postmeningitic hearing loss. METHODS: Children with bacterial meningitis were recruited from 21 centers. In the 48 hours before discharge from the hospital, all patients underwent a thorough audiologic assessment consisting of transient evoked OAEs, auditory brainstem responses (ABRs), otoscopy, and tympanometry. Hearing loss was defined as ABR threshold >/=30 dB. The results of OAE screening were compared with the gold standard of ABR threshold. RESULTS: Of 124 children recruited, we were able to perform both OAEs and ABRs on 110 children. Seven (6.3%) of the 110 children had ABR threshold >/=30 dB; 2 had sensorineural hearing loss and 5 had conductive hearing loss. At follow-up, hearing loss persisted in both cases of sensorineural hearing loss and no new cases were identified. All 7 children with hearing loss failed the OAE screening test. Ninety-four children with normal hearing thresholds passed the test, and 9 failed. Thus, the screening test had a sensitivity of 1.00 (95% confidence interval, 0.59 to 1.00), a specificity of 0.91 (0.85 to 0.97), a positive predictive value of 0. 44 (0.20 to 0.70), and a negative predictive value of 1.00 (0.96 to 1.00). CONCLUSIONS: OAE screening in children recovering from meningitis was found to be feasible and effective. The test was highly sensitive and reasonably specific. Inpatient OAE screening should allow early diagnosis of postmeningitic hearing loss and prompt auditory rehabilitation. 相似文献
64.
FJ O'Callaghan AC Clarke H Joffe B Keeton R Martin A Salmon RD Thomas JP Osborne 《Archives of disease in childhood》1998,78(2):159-162
This report highlights the association between tuberous sclerosis and Wolff-Parkinson-White syndrome. Ten patients with concurrent diagnoses of Wolff-Parkinson-White syndrome and tuberous sclerosis were identified. Wolff-Parkinson-White syndrome presented early in life, nine cases being diagnosed in the first year. Eight of the 10 cases were male. In eight cases, the syndrome was associated with supraventricular tachycardias, and in nine with cardiac rhabdomyomata. One child died from cardiac failure secondary to obstruction of the left ventricular outflow tract by a rhabdomyoma. Five of nine survivors showed resolution of Wolff-Parkinson-White syndrome on follow up. The accessory pathway was localised in nine patients from surface electrocardiograms: six children had left sided pathways and three had right sided pathways. 相似文献
65.
Iron-overload diseases frequently develop hepatocellular carcinoma. The
genotoxic mechanism whereby iron is involved in hepatocarcinogenesis might
involve an oxidative process via the intermediate production of reactive
oxygen species. This was presently investigated by examining kinetics of
formation and repair of DNA base lesions in primary rat hepatocyte cultures
supplemented with the iron chelate, ferric nitrilotriacetate Fe-NTA (10 and
100 microM). Seven DNA base oxidation products have been identified in DNA
extracts by gas chromatography- mass spectrometry, which showed a
predominance of oxidized-purines (8- oxo-guanine, xanthine, fapy-adenine,
2-oxo-adenine) above oxidized pyrimidines (5-OHMe-uracil, 5-OH-uracil,
5-OH-cytosine) in control cultures. All these DNA oxidation products
revealed a significant dose- dependent increase at 4 to 48 h after Fe-NTA
supplementation, among which fapy-adenine showed the highest increase and
5-OH-cytosine was the least prominent. Involvement of iron in this
oxidative process was established by a correlation between extent in DNA
oxidation and intracellular level of toxic low molecular weight iron. DNA
excision- repair activity was estimated by release of DNA oxidation
products in culture medium. All the seven DNA oxidation products were
detected in the medium of control cultures and showed basal repair
activity. This DNA repair activity was increased in a time- and
dose-dependent fashion with Fe-NTA. Oxidized-pyrimidines, among which was
5-OHMe-Uracil, were preferentially repaired, which explains the low levels
detected in oxidized DNA. Since oxidized bases substantially differed from
one another in terms of excision rates from cellular DNA, specific
excision- repair enzymes might be involved. Our findings, however,
demonstrate that even though DNA repair pathways were activated in
iron-loaded hepatocyte cultures, these processes were not stimulated enough
to prevent an accumulation of highly mutagenic DNA oxidative products in
genomic DNA. The resulting genotoxic effect of Fe-NTA might be relevant in
understanding the hepatocarcinogenic evolution of iron-overload diseases.
相似文献
66.
Flupirtine ameliorates ischaemic-like death of rat retinal ganglion cells by preventing calcium influx 总被引:4,自引:0,他引:4
The effect of flupirtine on the loss of retinal ganglion cells following transient elevation of intraocular pressure (experimental ischaemia) or NMDA-induced excitotoxicity was studied. Ischaemia (60 min) or intravitreal injection of NMDA (20 nmol) caused a decrease in Thy-1 mRNA and Thy-1 immunoreactivity which are associated with ganglion cells. Administration of flupirtine counteracted these changes. Moreover, flupirtine dose-dependently inhibited NMDA-induced 45Ca(2+) influx into cultured cortical neurones and retinal pieces in vitro with maximal inhibition being observed at 200 microM. A similar concentration of flupirtine failed to inhibit kainate-stimulated calcium influx into cultured cortical neurones. In addition, flupirtine had no significant effect on [3H]nitrendipine or [3H]diltiazem binding to cortical membranes. The present studies are consistent with previous findings which suggested flupirtine to act as a NMDA antagonist by a mechanism that still remains to be clarified. 相似文献
67.
Osborne R.H. Elsworth G.R. Sprangers M.A.G. Oort F.J. Hopper J.L. 《Quality of life research》2004,13(1):191-206
BACKGROUND: The Hospital Anxiety and Depression Scale (HADS) is frequently used in cancer studies, yet its utility for comparing people with cancer with people in the community is uncertain. METHODS: HADS scores were obtained from population-based samples of women with (n = 731) and without (n = 158) early-onset breast cancer. Psychometric properties were examined using differential item functioning (DIF) which is the presence of systematic group differences in certain response items independent of the trait being measured. RESULTS: Women with breast cancer scored lower than reference women on anxiety (mean (SD) 7.5 (4.3) vs. 8.2 (4.0); p = 0.06) and depression (3.3 (3.2) vs. 4.2 (3.0); p = 0.003). Group differences remained following adjustment for demographics. Time since diagnosis was not related to anxiety or depression scores. DIF was present in two anxiety and five depression items. Adjustment for DIF did not substantially change the anxiety or depression group differences. CONCLUSION: Specific sampling or DIF effects do not explain the observation that women with breast cancer have lower levels of anxiety and depression than population controls. The psychometric properties of the HADS appear to be acceptable in these groups. 相似文献
68.
69.
Patterns of resistance and incomplete response to docetaxel by gene expression profiling in breast cancer patients. 总被引:8,自引:0,他引:8
Jenny C Chang Eric C Wooten Anna Tsimelzon Susan G Hilsenbeck M Carolina Gutierrez Yee-Lu Tham Mamta Kalidas Richard Elledge Syed Mohsin C Kent Osborne Gary C Chamness D Craig Allred Michael T Lewis Helen Wong Peter O'Connell 《Journal of clinical oncology》2005,23(6):1169-1177
PURPOSE: Chemotherapy for operable breast cancer decreases the risk of death. Docetaxel is one of the most active agents in breast cancer, but resistance or incomplete response is frequent. PATIENTS AND METHODS: Core biopsies from 24 patients were obtained before treatment with neoadjuvant docetaxel (four cycles, 100 mg/m(2) every 3 weeks), and response was assessed after chemotherapy. After 3 months of neoadjuvant chemotherapy, surgical specimens (n = 13) were obtained, and laser capture microdissection (LCM; n = 8) was performed to enrich for tumor cells. From each core, surgical, and LCM specimen, sufficient total RNA (3 to 6 microg) was extracted for cDNA array analysis using the Affymetrix HgU95-Av2 GeneChip (Affymetrix, Santa Clara, CA). RESULTS: From the initial core biopsies, differential patterns of expression of 92 genes correlated with docetaxel response (P = .001). However, the molecular patterns of the residual cancers after 3 months of docetaxel treatment were strikingly similar, independent of initial sensitivity or resistance. This relative genetic homogeneity after treatment was observed in both LCM and non-LCM surgical specimens. The residual tumor after treatment in tumors that were initially sensitive indicates selection of a residual and resistant subpopulation of cells. The gene expression pattern was populated by genes involved in cell cycle arrest at G(2)M (eg, mitotic cyclins and cdc2) and survival pathways involving the mammalian target of rapamycin. CONCLUSION: A specific and consistent gene expression pattern was found in residual tumors after docetaxel treatment. These profiles provide therapeutic targets that could lead to improved treatment. 相似文献
70.
Gang Chen Alexander J Chan Josiah I Chung Jessica C Jang Lisa C Osborne Meera G Nair 《Gut microbes》2014,5(3):363-368
Citrobacter rodentium infection is a murine model of pathogenic Escherichia coli infection that allows investigation of the cellular and molecular mechanisms involved in host-protective immunity and bacterial-induced intestinal inflammation. We recently demonstrated that following C. rodentium infection, the absence of Resistin-Like Molecule (RELM) α resulted in attenuated Th17 cell responses and reduced intestinal inflammation with minimal effects on bacterial clearance. In this addendum, we investigated the cytokine modulatory effects of RELMα and RELMα expression in the intestinal mucosa following C. rodentium infection. We show that in addition to promoting Th17 cytokine responses, RELMα inhibits Th2 cytokine expression and Th2-cytokine effector macrophage responses in the C. rodentium-infected colons. Second, utilizing reporter C. rodentium, we examined RELMα expression and macrophage recruitment at the host pathogen interface. We observed infection-induced macrophage infiltration and RELMα expression by intestinal epithelial cells. The influence of infection-induced RELMα on macrophage recruitment in the intestine is discussed. 相似文献