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11.
A NOTCH1 gene copy number gain is a prognostic indicator of worse survival and a predictive biomarker to a Notch1 targeting antibody in colorectal cancer 下载免费PDF全文
John J. Arcaroli W.M. Tai Ryan McWilliams Stacey Bagby Patrick J. Blatchford Marileila Varella‐Garcia Alicia Purkey Kevin S. Quackenbush Eun‐Kee Song Todd M. Pitts Dexiang Gao Chris Lieu Martine McManus Aik Choon Tan Xianxian Zheng Qin Zhang Mark Ozeck Peter Olson Zhi‐Qin Jiang Scott Kopetz Antonio Jimeno Stephen Keysar Gail Eckhardt Wells A. Messersmith 《International journal of cancer. Journal international du cancer》2016,138(1):195-205
Dysregulation of the Notch1 receptor has been shown to facilitate the development and progression of colorectal cancer (CRC) and has been identified as an independent predictor of disease progression and worse survival. Although mutations in the NOTCH1 receptor have not been described in CRC, we have previously discovered a NOTCH1 gene copy number gain in a portion of CRC tumor samples. Here, we demonstrated that a NOTCH1 gene copy number gain is significantly associated with worse survival and a high percentage of gene duplication in a cohort of patients with advanced CRC. In our CRC patient‐derived tumor xenograft (PDTX) model, tumors harboring a NOTCH1 gain exhibited significant elevation of the Notch1 receptor, JAG1 ligand and cleaved Notch1 activity. In addition, a significant association was identified between a gain in NOTCH1 gene copy number and sensitivity to a Notch1‐targeting antibody. These findings suggest that patients with metastatic CRC that harbor a gain in NOTCH1 gene copy number have worse survival and that targeting this patient population with a Notch1 antibody may yield improved outcomes. 相似文献
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M D Ene P J Williamson T K Daneshmend N R Blatchford 《British journal of clinical pharmacology》1984,17(2):173-175
Eight healthy female subjects were each given (a) ketoconazole 400 mg orally, (b) ketoconazole 400 mg as a single vaginal pessary, (c) ketoconazole 800 mg as two vaginal pessaries, and (d) ketoconazole 1200 mg as three vaginal pessaries. The area under the plasma concentration time curve (AUC) after the oral dose was 51.41 +/- 10.99 mg l-1 h (mean +/- s.d.) and the half-life of ketoconazole was 2.98 +/- 1.41 h. The AUCs after vaginal administration were 0.27 +/- 0.14, 0.52 +/- 0.25, and 0.43 +/- 0.22 mg-1 l h following the 400, 800 and 1200 mg pessaries respectively. Systemic absorption of single doses of vaginally administered ketoconazole appears to be negligible in the absence of vaginal infection. There were no local or systemic side effects related to ketoconazole in these healthy volunteers. 相似文献
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马蓝的化学成分研究 总被引:15,自引:0,他引:15
Seven compounds have been isolated from the whole plant of Strobilanthes cusia (Nees) O. Ktze. Three of them are triterpenes (Ⅰ~Ⅲ), two are indole alkaloids (Ⅳ, Ⅴ), two are quinazolinone alkaloids (Ⅵ, Ⅶ). On the basis of spectral analysis and physicochemical properties, their structures were established as lupeol (Ⅰ), betulin (Ⅱ), lupenone (Ⅲ), indigo (Ⅳ), indirubin (Ⅴ), 4 (3H)-quinazolinone (Ⅵ), 2, 4 (1H, 3H)-quinazolinedione (Ⅶ). Ⅵ and Ⅶ were found from natural plant for the first time.The results of the pharmacological tests demonstrate that compound Ⅴ has anticancer activity and compound Ⅵ has hypotensive action. Compound Ⅶ can be quantitatively determined by HPLC, which may serve as a quality control standard for materia medica and its preparations. Compounds Ⅵ and Ⅶ have been confirmed by means of synthesis. 相似文献
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B19 parvovirus is the etiologic agent of fifth disease and transient aplastic crisis. In natural infections, B19 antigen and DNA have been detected in sera early in the course of aplastic crisis and only rarely in fifth disease. We have found B19 DNA in circulating cells of infected patients by DNA dot blot with a virus-specific probe: in four of four sickle cell patients with aplastic crisis, in one asymptomatic sibling, and in one normal adult with fifth disease. Only two of the sera showed B19 DNA. High-molecular weight intermediate forms were detected by Southern analysis of DNA extracted from cells, thus indicating active replication of virus in cells rather than passive adsorption to their surface membranes. Separation of cells into high- and low-density fractions resulted in a concentration of the virus DNA in the granulocytic fraction. 相似文献
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Eosinophil autofluorescence and its use in isolation and analysis of human eosinophils using flow microfluorometry 总被引:5,自引:1,他引:5
Unstained human eosinophils exhibit unusually bright autofluorescence, which allows them to be distinguished from other leukocytes using fluorescence microscopy. Eosinophil fluorescence is associated with the cytoplasmic granules of the cells. Eosinophil granule extracts, containing an as-yet-undefined eosinophil fluorescence factor, exhibited excitation maxima at 370 nm and 450 nm, with maximum emission at 520 nm. Eosinophils adhering to opsonized parasites in vitro deposit fluorescent material onto the parasite surface. Eosinophil fluorescence was of sufficient intensity to allow the preparation of viable, highly enriched (greater than or equal to 98%), eosinophil suspensions from peripheral blood of normal and eosinophilic donors using a fluorescence- activated cell sorter. Quantitative studies of eosinophil autofluorescence were performed using flow microfluorometry. Fluorescence intensity of blood eosinophils from normal volunteers and eosinophilic patients varied inversely with the log of the donor's absolute eosinophil count regardless of clinical diagnosis. 相似文献
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P. M. Falk M.D. N. C. Gupta M.D. Dr. A. G. Thorson M.D. M. P. Frick M.D. B. M. Boman M.D. Ph.D. M. A. Christensen M.D. G. J. Blatchford M.D. 《Diseases of the colon and rectum》1994,37(2):153-156
PURPOSE: Positron emission tomography (PET) is an imaging technique based onin vivo cellular metabolism. Increased glucose metabolism in neoplastic cells is detected by using fluorine-18 deoxyglucose. In an ongoing pilot study to determine the usefulness of this technique, PET is compared with computerized tomography (CT) for the preoperative staging of colorectal carcinoma. METHODS: Sixteen patients were evaluated with both PET and CT of the abdomen and pelvis. Results were compared with operative and histopathologic findings. Fifteen malignant lesions were found in 16 patients by histology. PET had a positive predictive value of 93 percent and a negative predictive value of 50 percent. By comparison CT had a positive predictive value of 100 percent and a negative predictive value of 27 percent. CONCLUSIONS: These preliminary results indicate that PET has increased sensitivity for staging colorectal carcinoma, whereas CT has higher specificity. The predictive value of a positive PET compares favorably with CT. Furthermore, the predictive accuracy for detection of colorectal carcinoma is 83 percent for PET and 56 percent for CT.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, San Francisco, California, June 7 to 12, 1992.Presented in part in the Nebraska Medical Journal, February 1993. 相似文献
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D McWhirter M den Dulk M Terlizzo HZ Malik SW Fenwick GJ Poston 《Annals of the Royal College of Surgeons of England》2013,95(8):e136-e138
A 74-year old man underwent a radical cholecystectomy for presumed gallbladder cancer. The histology of the resected specimen in fact revealed the lesion to be metastatic renal cell carcinoma from his resected right nephrectomy performed 14 years previously. 相似文献