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排序方式: 共有10000条查询结果,搜索用时 15 毫秒
961.
Richard B. Lock Bruce S. Thompson Daniel M. Sullivan Lolita Stribinskiene 《Cancer chemotherapy and pharmacology》1997,39(5):399-409
Protein kinase inhibitors have demonstrated potential for use in the therapy of human cancers, in particular leukemia. Staurosporine,
a protein kinase inhibitor with broad specificity, enhances the cytotoxic effects of various antitumor agents with different
modes of action. The topoisomerase II inhibitor, etoposide, has shown clinical activity against a wide range of tumor types.
Purpose: The purpose of this study was to assess the effects of staurosporine on etoposide-induced cell death processes in a human
tumor of epithelial origin. Methods: Modulation of etoposide-induced apoptosis by staurosporine in HeLa cells was assessed by cell morphology, extraction of
low molecular weight DNA, quantitation of DNA-protein complexes, and measurements of rates of DNA synthesis. The effects on
cellular genes implicated in apoptosis were determined by Northern and Western blotting, along with assays of cyclin-dependent
kinase activities. Results: Stauro- sporine exhibited a two- to three-fold potentiation of apoptosis caused by etoposide in HeLa cells when ap- plied
concurrently, or immediately following etoposide removal, but did not alter the quantity of DNA-protein complexes produced
by etoposide. Etoposide-induced apoptosis, and its potentiation by staurosporine, were associated with reduced c-myc expression, and a moderate increase in p21WAF1/CIP1 mRNA and protein levels. Inhibitors of cyclic AMP-dependent protein kinase and protein kinase C, which exhibit greater specificity
than staurosporine, were without effect on apoptosis caused by etoposide, whereas use of the tyrosine phosphatase inhibitor,
vanadate, resulted in its abrogation. The potentiation of etoposide-induced apoptosis by staurosporine was associated with
a significant increase in cyclin A-dependent kinase activity. In addition, etoposide caused substantial inhibition of DNA
synthesis. Conclusion: These results indicate that staurosporine potentiates apoptosis through events which occur downstream of DNA damage, and
implicate unscheduled activation of cyclin A-dependent kinase during inhibition of DNA synthesis as a possible cause.
Received: 28 November 1995/Accepted: 8 July 1996 相似文献
962.
A. Kate Hole Abbes Belkhiri Linda S. Snell Peter H. Watson 《Breast cancer research and treatment》1997,43(2):165-173
To understand the relationship between CD44 gene expressionand an established variable associated with aggressive behaviourin human breast cancer, we have studied apanel of 6 breast cell lines and 40breast tumors selected primarily on the basis ofestrogen receptor (ER) status. CD44s (standard form) mRNAwas assessed by semi-quantitative RT-PCR, and CD44 variantsincorporating exon v7 or v10 were studied byRT-PCR and Southern blot. While CD44 expression wasnot influenced by estrogen in ER+ve MCF-7 cells,CD44s expression was slightly higher (up to 2fold) in ER–ve cells but there was amarked decrease in the range of CD44 variantsincorporating exons v7 or v10. In microdissected tumors,the levels of CD44s showed no correlation withER status but the pattern of expression oflarger forms of CD44 incorporating variant exons v7and v10 was significantly different (p=0.005and p=0.015, respectively) between ER+ve andER–ve tumors, reflecting the pattern seen in thecell lines. These findings suggest that the profileof CD44 expression in breast cancer may reflectcellular differentiation as indicated by the ER phenotype.The influence of these differences in CD44 expressionon the increased metastatic potential of ER negativebreast cancer remains to be determined. 相似文献
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967.
Wei Yue Steven J. Santner Shigeru Masamura Ji-Ping Wang Laurence M. Demers Christopher Hamilton Richard J. Santen 《Breast cancer research and treatment》1998,49(1):S1-S7
Estradiol stimulates the growth of breast tumor cells in both pre- and post menopausal women. Following the menopause, the levels of estradiol in breast tumor tissues are similar to those from tumors obtained prior to cessation of ovarian function, even though plasma estrogen levels are 10–50 fold lower in post- than in premenopausal women. These observations suggested the possibility of enhanced estradiol uptake from plasma or in situ synthesis in post-menopausal women. We systematically studied these possibilities in a series of model systems. Initially we demonstrated a very high affinity estradiol binding site in tissues from castrated rats. Enhanced uptake occurred under conditions of low plasma estrogen levels when compared to animals with higher estradiol levels. In situ synthesis also occurred both through the sulfatase and aromatase pathways. In further studies, we compared uptake from plasma with in situ synthesis via aromatase in a nude mouse model. Under the conditions utilized, in situ synthesis resulted in much higher tissue estradiol levels and tumor growth rates than did uptake from plasma. During these studies we demonstrated that tumors deprived of estradiol developed mechanisms rendering them more sensitive to estrogen. This involved the ability of cells to adapt to estradiol deprivation to allow them to be responsive to four log lower amounts of estrogen than when studied under wild type conditions. In addition, cells adapted by increasing their level of aromatase and thus developing the capability to become more sensitive to estrogen precursors. Taken together, these studies demonstrate that breast cancer tissue is highly plastic and can adapt to conditions of estrogen deprivation via a variety of mechanisms. 相似文献
968.
969.
Cutaneous manifestations of malignancy are not uncommon, especially in advanced disease. They may also occur early in malignant disease or they may even signify recurrence particularly if they are paraneoplastic in nature. Clinical diagnosis can be difficult because of the wide spectrum of appearance of these lesions, and, in many cases, because of the lack of an identifiable underlying primary. Presented here is the case of a 65-year-old woman with multiple inflammatory cutaneous metastases, which were sclerodermoid in nature. These appeared 14 months after initial diagnosis of adenocarcinoma of unknown primary (ACUP) and signified the beginning of a rapid deterioration in her condition. The coexistence of limited systemic sclerosis (scleroderma) and ACUP initially raised several interesting diagnostic possibilities. Adenocarcinoma of unknown primary and the sclerodermoid reaction in malignancy are discussed. 相似文献
970.