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131.
Phosphatidylinositol 3-kinases (PI3Ks) are key molecules in the signal transduction pathways initiated by the binding of extracellular signals to their cell surface receptors. The PI3K family of enzymes comprises eight catalytic isoforms subdivided into three classes and control a variety of cellular processes including proliferation, growth, apoptosis, migration and metabolism. Deregulation of the PI3K pathway has been extensively investigated in connection to cancer, but is also involved in other commonly occurring diseases such as chronic inflammation, autoimmunity, allergy, atherosclerosis, cardiovascular and metabolic diseases. The fact that the PI3K pathway is deregulated in a large number of human diseases, and its importance for different cellular responses, makes it an attractive drug target. Pharmacological PI3K inhibitors have played a very important role in studying cellular responses involving these enzymes. Currently, a wide range of selective PI3K inhibitors have been tested in preclinical studies and some have entered clinical trials in oncology. However, due to the complexity of PI3K signaling pathways, developing an effective anti-cancer therapy may be difficult. The biggest challenge in curing cancer patients with various signaling pathway abnormalities is to target multiple components of different signal transduction pathways with mechanism-based combinatorial treatments. In this article we will give an overview of the complex role of PI3K isoforms in human diseases and discuss their potential as drug targets. In addition, we will describe the drugs currently used in clinical trials, as well as promising emerging candidates. 相似文献
132.
Angiogenesis Markers Quantification in Breast Cancer and Their Correlation with Clinicopathological Prognostic Variables 总被引:1,自引:0,他引:1
Rykala J Przybylowska K Majsterek I Pasz-Walczak G Sygut A Dziki A Kruk-Jeromin J 《Pathology oncology research : POR》2011,17(4):809-817
Tumoural angiogenesis is essential for the growth and spread of breast cancer cells. Therefore the aim of this study was to
assess the diagnostic performance of angiogenesis markers in tumours and there reflecting levels in serum of breast cancer
patients. Angiogenin, Ang2, fibroblast growth factor basic, intercellular adhesion molecule (ICAM)-1, keratinocyte growth
factor (KGF), platelet-derived growth factor-BB, and VEGF-A were measured using a FASTQuant angiogenic growth factor multiplex
protein assay. We observed that breast cancer tumours exhibited high levels of PDGF-BB, bFGF and VEGF, and extremely high
levels of TIMP-1 and Ang-2, whereas in serum we found significantly higher levels of Ang-2, PDGF-BB, bFGF, ICAM-1 and VEGF
in patients with breast cancer compared to the benign breast diseases patients. Moreover, some of these angiogenesis markers
evaluated in tumour and serum of breast cancer patients exhibited association with standard clinical parameters, ER status
as well as MVD of tumours. Angiogenesis markers play important roles in tumour growth, invasion and metastasis. Our results
suggest that analysis of angiogenesis markers in tumour and serum of breast cancer patients using multiplex protein assay
can improve diagnosis and prognosis in this diseases. 相似文献
133.
Nyberg L Salami A Andersson M Eriksson J Kalpouzos G Kauppi K Lind J Pudas S Persson J Nilsson LG 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(52):22682-22686
Cross-sectional estimates of age-related changes in brain structure and function were compared with 6-y longitudinal estimates. The results indicated increased sensitivity of the longitudinal approach as well as qualitative differences. Critically, the cross-sectional analyses were suggestive of age-related frontal overrecruitment, whereas the longitudinal analyses revealed frontal underrecruitment with advancing age. The cross-sectional observation of overrecruitment reflected a select elderly sample. However, when followed over time, this sample showed reduced frontal recruitment. These findings dispute inferences of true age changes on the basis of age differences, hence challenging some contemporary models of neurocognitive aging, and demonstrate age-related decline in frontal brain volume as well as functional response. 相似文献
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135.
Alistair T. Pagnamenta Rebecca S. Belles Bonnie Anne Salbert Ingrid M. Wentzensen Maria J. Guillen Sacoto Francis Jeshira Reynoso Santos Alesky Caffo Matteo Ferla Benito Banos-Pinero Karolina Pawliczak Mina Makvand Hossein Najmabadi Genomics England Research Consortium Reza Maroofian Tracy Lester Ana Lucia Yanez-Felix Camilo E. Villarroel-Cortes Fan Xia Khowla Al Fayez Amal Al Hashem Deborah Shears Melita Irving Amaka C. Offiah Ariana Kariminejad Jenny C. Taylor 《Clinical genetics》2023,104(1):121-126
PKDCC encodes a component of Hedgehog signalling required for normal chondrogenesis and skeletal development. Although biallelic PKDCC variants have been implicated in rhizomelic shortening of limbs with variable dysmorphic features, this association was based on just two patients. In this study, data from the 100 000 Genomes Project was used in conjunction with exome sequencing and panel-testing results accessed via international collaboration to assemble a cohort of eight individuals from seven independent families with biallelic PKDCC variants. The allelic series included six frameshifts, a previously described splice-donor site variant and a likely pathogenic missense variant observed in two families that was supported by in silico structural modelling. Database queries suggested that the prevalence of this condition is between 1 of 127 and 1 of 721 in clinical cohorts with skeletal dysplasia of unknown aetiology. Clinical assessments, combined with data from previously published cases, indicate a predominantly upper limb involvement. Micrognathia, hypertelorism and hearing loss appear to be commonly co-occurring features. In conclusion, this study strengthens the link between biallelic inactivation of PKDCC and rhizomelic limb-shortening and will enable clinical testing laboratories to better interpret variants in this gene. 相似文献
136.
Souza Matheus Albino Ricci Rafaela Bischoff Karolina Frick Reuter Eduarda Ferreira Eduarda Rizzon Dallepiane Felipe Gomes Quevedo Laura Mezzalira Pereira Luiz Henrique Bergoli Bischoff Luiza Frick Hofstetter Mariana Gabriela Brammer Mariana Patussi Bernardes Natália Miranda Bervian Juliane 《Clinical oral investigations》2023,27(4):1659-1664
Clinical Oral Investigations - The aim of this study was to evaluate the effectiveness of ultrasonic activation (US) over glycolic acid on microhardness, cohesive strength, flexural strength, and... 相似文献
137.
Krzysztof Boczar MD PhD Andrzej Ząbek MD PhD Karolina Golińska-Grzybała MD PhD Agnieszka Sławuta MD PhD Maciej Dębski MD PhD Jacek Gajek MD PhD Katarzyna Holcman MD PhD Andrzej Gackowski MD PhD Jacek Lelakowski MD PhD Barbara Małecka MD PhD 《Echocardiography (Mount Kisco, N.Y.)》2023,40(10):1068-1078
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140.
Palucka AK Ueno H Fay J Banchereau J 《Journal of immunotherapy (Hagerstown, Md. : 1997)》2008,31(9):793-805
Cancer immunotherapy seeks to mobilize a patient's immune system for therapeutic benefit. It can be passive, that is, transfer of immune effector cells (T cells) or proteins (antibodies), or active, that is, vaccination. Early clinical trials testing vaccination with ex vivo generated dendritic cells (DCs) pulsed with tumor antigens provide a proof-of-principle that therapeutic immunity can be elicited. Yet, the clinical benefit measured by regression of established tumors in patients with stage IV cancer has been observed in a fraction of patients only. The next generation of DC vaccines is expected to generate large numbers of high avidity effector CD8 T cells and to overcome regulatory T cells and suppressive environment established by tumors, a major obstacle in metastatic disease. Therapeutic vaccination protocols will combine improved DC vaccines with chemotherapy to exploit immunogenic chemotherapy regimens. We foresee adjuvant vaccination in patients with resected tumors but at high risk of relapse to be based on in vivo targeting of DCs with fusion proteins containing anti-DCs antibodies, antigens from tumor stem/propagating cells, and DC activators. 相似文献