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41.
Katrin Lamszus Ulrike Ulbricht Jakob Matschke Marc A Brockmann Regina Fillbrandt Manfred Westphal 《Clinical cancer research》2003,9(4):1399-1405
PURPOSE: Vascular endothelial growth factor (VEGF)-A isa key mediator of angiogenesis in malignant gliomas. Soluble VEGF receptor 1 (sVEGFR-1) can complex VEGF-A and reduce its bioavailability. In several animal models sVEGFR-1 inhibited angiogenesis and tumor growth. We analyzed the levels of endogenous sVEGFR-1 in gliomas of different malignancy grades in relation to tumor vascularity and VEGF-A. EXPERIMENTAL DESIGN: The concentration of sVEGFR-1 was determined by ELISA in 104 gliomas and normal brain. Levels of sVEGFR-1 were compared with malignancy grade, microvessel density, and VEGF-A concentration. Effects of sVEGFR-1 on glioma extract-induced endothelial cell chemotaxis were analyzed in vitro. RESULTS: The concentration of sVEGFR-1 correlated with the malignancy grade and was 12-fold higher in glioblastomas than in diffuse astrocytomas (P < 0.001), with intermediate levels for anaplastic astrocytomas. VEGF-A levels were 30-fold higher (P < 0.001) in glioblastomas than in diffuse astrocytomas. The sVEGFR-1:VEGF-A ratio was 0.27 in glioblastomas and 0.70 in diffuse astrocytomas. Both sVEGFR-1 and VEGF-A correlated with microvessel density (P < 0.001) and with each other (P < 0.001); sVEGFR-1 and VEGF-A also correlated with each other when only glioblastomas were analyzed (P = 0.001). In vitro, recombinant sVEGFR-1 inhibited endothelial cell chemotaxis induced by tumor extracts. CONCLUSIONS: Although absolute levels of sVEGFR-1 are increased in the more malignant gliomas, the sVEGFR-1:VEGF-A ratio is decreased 2.6-fold in glioblastomas compared with diffuse astrocytomas, suggesting that the ensuing increased bioavailability of VEGF-A favors angiogenesis. The inhibition of tumor extract-induced endothelial chemotaxis by sVEGFR-1 suggests that sVEGFR-1 could be useful as an angiogenesis inhibitor in the specific context of human gliomas. 相似文献
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Katrin Lamszus Marc A Brockmann Carmen Eckerich Peter Bohlen Chad May Ulrich Mangold Regina Fillbrandt Manfred Westphal 《Clinical cancer research》2005,11(13):4934-4940
PURPOSE: Inhibition of angiogenesis can influence tumor cell invasion and metastasis. We previously showed that blockade of vascular endothelial growth factor receptor-2 (VEGFR-2) with the monoclonal antibody DC101 inhibited intracerebral glioblastoma growth but caused increased tumor cell invasion along the preexistent vasculature. In the present study, we attempted to inhibit glioma cell invasion using a monoclonal antibody against the epidermal growth factor receptor (EGFR), which in the context of human glioblastomas, has been implicated in tumor cell invasion. In addition, we analyzed whether blockade of vascular endothelial (VE)-cadherin as a different antiangiogenic target could also inhibit glioblastoma angiogenesis and growth. EXPERIMENTAL DESIGNS: Nude mice who received intracerebral glioblastoma xenografts were treated using monoclonal antibodies against VEGFR-2 (DC101), EGFR (C225), and VE-cadherin (E4G10) either alone or in different combinations. RESULTS: Increased tumor cell invasion provoked by DC101 monotherapy was inhibited by 50% to 66% by combined treatment with C225 and DC101. C225 inhibited glioblastoma cell migration in vitro, but had no effect on the volume of the main tumor mass or on tumor cell proliferation or apoptosis in vivo, either alone or in combination with DC101. The anti-VE-cadherin monoclonal antibody E4G10 was a weaker inhibitor of tumor angiogenesis and growth than DC101, and also caused a weaker increase in tumor cell invasion. CONCLUSIONS: Inhibition of angiogenesis achieved by blocking either VEGFR-2 or VE-cadherin can cause increased glioma cell invasion in an orthotopic model. Increased tumor cell invasion induced by potent inhibition of angiogenesis with DC101 could be inhibited by simultaneous blockade of EGFR. 相似文献
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Katinka Breuer Korbinian M. Riedhammer Nicole Müller Birthe Schaidinger Gregor Dombrowsky Sven Dittrich Susanne Zeidler Ulrike M. M. Bauer Dominik S. Westphal Thomas Meitinger Tikam Chand Dakal Marc-Phillip Hitz Johannes Breuer Heiko Reutter Alina C. Hilger Julia Hoefele 《European journal of human genetics : EJHG》2022,30(8):946
The birth prevalence of laterality defects is about 1.1/10,000 comprising different phenotypes ranging from situs inversus totalis to heterotaxy, mostly associated with complex congenital heart defects (CHD) and situs abnormalities such as intestinal malrotation, biliary atresia, asplenia, or polysplenia. A proportion of laterality defects arise in the context of primary ciliary dyskinesia (PCD) accompanied by respiratory symptoms or infertility. In this study, exome sequencing (ES) was performed in 14 case-parent trios/quattros with clinical exclusion of PCD prior to analysis. Moreover, all cases and parents underwent detailed clinical phenotyping including physical examination, echocardiography by a skilled paediatric cardiologist and abdominal ultrasound examinations not to miss mildly affected individuals. Subsequent survey of the exome data comprised filtering for monoallelic de novo, rare biallelic, and X-linked recessive variants. In two families, rare variants of uncertain significance (VUS) in PKD1L1 and ZIC3 were identified. Both genes have been associated with laterality defects. In two of the remaining families, biallelic variants in LMBRD1 and DNAH17, respectively, were prioritized. In another family, an ultra-rare de novo variant in WDR47 was found. Extensive exome survey of 2,109 single exomes of individuals with situs inversus totalis, heterotaxy, or isolated CHD identified two individuals with novel monoallelic variants in WDR47, but no further individuals with biallelic variants in DNAH17 or LMBRD1. Overall, ES of 14 case-parent trios/quattros with cardiovascular laterality defects identified rare VUS in two families in known disease-associated genes PKD1L1 and ZIC3 and suggests DNAH17, LMBRD1, and WDR47 as potential genes involved in laterality defects.Subject terms: Disease genetics, Genetic counselling, Biological sciences 相似文献
46.
A retrospective review of all patients older than 35 who underwent elective single blastocyst transfer was performed. Twenty-three of the 45 patients (51.1%) have an ongoing pregnancy or liveborn delivery, with a mean age of 37.3 years, demonstrating a clear role for elective single transfer in this relatively older IVF population. 相似文献
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48.
Transvaginal ultrasound or MRI for diagnosis of adenomyosis 总被引:1,自引:0,他引:1
PURPOSE OF REVIEW: Transvaginal ultrasound and MRI are used to diagnose adenomyosis. This review summarizes the current evidence on the diagnostic accuracy of these techniques. RECENT FINDINGS: The image resolution of both transvaginal ultrasound and MRI is effective for the diagnosis of adenomyosis. In a limited number of well-designed studies the diagnostic efficiency of MRI and transvaginal ultrasound were almost in line. With transvaginal ultrasound, considerable training is needed to recognize the distinct ultrasound pattern in the diagnosis of adenomyosis. The findings in MRI are less observer dependent, but still somewhat dependent on an MRI observer who is expert in gynecologic imaging. SUMMARY: Transvaginal ultrasound is the natural first choice of image modality when investigating pelvic pain or menstrual disorders, but correct diagnosis of adenomyosis is dependent on sonographers trained in pattern recognition of adenomyosis. When transvaginal ultrasound provides indefinite findings or when dealing with difficult cases with coexistence of other abnormalities (myomas and severe endometriosis), MRI may add information and increase the diagnostic performance. 相似文献
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Holthusen Diepgen Oppenheimer Griesbach Günther Schübel Koenigsfeld Vaternahm Gottschalk Martini Blumenfeldt Friedemann Edens Magnus-Alsleben Westphal Eisner-Behrend Sperling Wohlwill Weigert J. Jadassohn Buschke sen Jaffé Valentin Meyer-Burgdorff Gruhle Goldstein 《Journal of molecular medicine (Berlin, Germany)》1931,10(46):2140-2147