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排序方式: 共有371条查询结果,搜索用时 15 毫秒
41.
David Yu Greenblatt Max Cayo Li Ning Renata Jaskula-Sztul Megan Haymart Muthusamy Kunnimalaiyaan Herbert Chen 《Journal of gastrointestinal surgery》2007,11(11):1515-1520
Carcinoid cancers arise from the neuroendocrine cell system of the gastrointestinal tract, lungs, and other organs. Hepatic
metastases are common, and patients often suffer from endocrinopathies secondary to tumor secretion of various hormones and
peptides. As complete surgical resection is often not possible because of widespread disease, new therapeutic and palliative
treatments are needed. In this study, we characterized the effects of suberoyl bishydroxamic acid (SBHA), a histone deacetylase
inhibitor, on the growth and neuroendocrine phenotype of carcinoid cancer cells. SBHA treatment of human gastrointestinal
and pulmonary carcinoid cancer cells resulted in a dose-dependent inhibition of cell proliferation. Western blot analysis
showed a decrease in cyclin D1 and an increase in p21 and p27, indicating that the mechanism of this growth inhibition is
cell cycle arrest. Furthermore, SBHA treatment suppressed two neuroendocrine tumor markers, chromogranin A and achaete-scute
complex-like 1. These changes in the growth and neuroendocrine phenotype of carcinoid cells were associated with activation
of the Notch1 signaling cascade. We conclude that SBHA shows promise as a potential anticancer agent for the treatment of
patients with advanced carcinoid tumor disease.
This paper was presented at the 48th Annual Meeting of the Society for Surgery of the Alimentary Tract, May 19–23, 2007, Washington,
DC, USA. 相似文献
42.
43.
Herman SE Lapalombella R Gordon AL Ramanunni A Blum KA Jones J Zhang X Lannutti BJ Puri KD Muthusamy N Byrd JC Johnson AJ 《Blood》2011,117(16):4323-4327
In patients with chronic lymphocytic leukemia (CLL), lenalidomide can promote humoral immune responses but also induces a distinct disease-specific toxicity of tumor flare and cytokine release. These CLL-specific events result from increased expression of costimulatory molecules on B cells. Here we demonstrate that lenalidomide activation of CLL cells depends on the phosphatidylinositol 3-kinase p110δ (PI3K-δ) pathway. Inhibition of PI3K-δ signaling by the PI3K-δ-inhibiting drug, CAL-101, or by siRNA knockdown of p110δ, abrogates CLL cell activation, costimulatory molecule expression, and vascular endothelial growth factor and basic fibroblast growth factor gene expression that is induced by lenalidomide. In addition, CAL-101 attenuates lenalidomide-mediated increases in immunoglobulin M production by normal B cells. Collectively, these data demonstrate the importance of PI3K-δ signaling for lenalidomide immune modulation. These findings may guide development of strategies for the treatment of CLL that combine lenalidomide with CAL-101, with other inhibitors of the PI3K-δ pathway, or with other agents that target downstream kinases of this signaling pathway. 相似文献
44.
Alinari L Yu B Christian BA Yan F Shin J Lapalombella R Hertlein E Lustberg ME Quinion C Zhang X Lozanski G Muthusamy N Prætorius-Ibba M O'Connor OA Goldenberg DM Byrd JC Blum KA Baiocchi RA 《Blood》2011,117(17):4530-4541
Mantle cell lymphoma (MCL) is an aggressive B-cell malignancy with a median survival of 3 years despite chemoimmunotherapy. Rituximab, a chimeric anti-CD20 monoclonal antibody (mAb), has shown only modest activity as single agent in MCL. The humanized mAb milatuzumab targets CD74, an integral membrane protein linked with promotion of B-cell growth and survival, and has shown preclinical activity against B-cell malignancies. Because rituximab and milatuzumab target distinct antigens and potentially signal through different pathways, we explored a preclinical combination strategy in MCL. Treatment of MCL cell lines and primary tumor cells with immobilized milatuzumab and rituximab resulted in rapid cell death, radical oxygen species generation, and loss of mitochondrial membrane potential. Cytoskeletal distrupting agents significantly reduced formation of CD20/CD74 aggregates, cell adhesion, and cell death, highlighting the importance of actin microfilaments in rituximab/milatuzumab-mediated cell death. Cell death was independent of caspase activation, Bcl-2 family proteins or modulation of autophagy. Maximal inhibition of p65 nuclear translocation was observed with combination treatment, indicating disruption of the NF-κB pathway. Significant in vivo therapeutic activity of combination rituximab and milatuzumab was demonstrated in a preclinical model of MCL. These data support clinical evaluation of combination milatuzumab and rituximab therapy in MCL. 相似文献
45.
46.
Heidt S San Segundo D Shankar S Mittal S Muthusamy AS Friend PJ Fuggle SV Wood KJ 《Transplantation》2011,92(1):1-9
Currently, acute allograft rejection can only be detected reliably by deterioration of graft function confirmed by allograft biopsy. A huge drawback of this method of diagnosis is that substantial organ damage has already taken place at the time that rejection is diagnosed. Discovering and validating noninvasive biomarkers that predict acute rejection, and chronic allograft dysfunction, is of great importance. Many studies have investigated changes in the peripheral blood in an attempt to find biomarkers that reflect changes in the graft directly or indirectly. Herein, we will review the promises and limitations of the peripheral blood biomarkers that have been described in the literature so far. 相似文献
47.
48.
Kirthi Koka Andrea Tongbram Bipasha Mukherjee Raman Muthusamy Azhahia Nambi Jyotirmay Biswas 《Orbit (Amsterdam, Netherlands)》2013,32(6):503-506
Thelazia callipaeda is a rare parasitic infestation caused by spiruroid nematode of the genus Thelazia. We report a case of a 74-year-old gentleman who presented with a painless swelling of left lower lid since 15 days. Examination revealed a firm mobile mass along the inferior orbital rim. Magnetic Resonance Imaging showed a well-defined preseptal cystic lesion and Ultrasound screening revealed multiple mobile worms within. Patient underwent cyst excision in toto under local anesthesia. Four long refractile worms were isolated from within the cyst cavity. Species identification confirmed the parasite as Thelazia callipaeda. Periocular thelaziasis usually presents as free floating worms in the conjunctival sac, anterior chamber or vitreous cavity. It is important to be aware of this rare entity which should be considered as a differential diagnosis in endemic areas. 相似文献
49.
Palani Kirubakaran Karthikeyan Muthusamy Kh. Dhanachandra Singh Selvaraman Nagamani 《Medicinal chemistry research》2013,22(8):3812-3822
The 3-phosphoinositide-dependent protein kinase-1 (PDK1) is an imminent target for discovering novel anticancer drugs. In order to understand the structure–activity correlation of naphthyridine-based PDK-1 inhibitors, we have carried out a combined pharmacophore, three-dimensional quantitative structure–activity relationship (3D-QSAR), and molecular docking studies. The study has resulted in six point pharmacophore models with four hydrogen bond acceptors (A), one hydrogen bond donor (D), and one aromatic ring (R) are used to derive a predictive atom-based 3D-QSAR model. The generated 3D-QSAR model shows that the alignment has good correlation coefficient for the training set compounds which comprises the values of R 2 = 0.96, SD = 0.2, and F = 198.2. Test set compounds shows Q 2 = 0.84, RMSE = 0.56, and Pearson-R = 0.84. The external validation was carried out to validate the predicted QSAR model which shows good predictive power of $ r_{m}^{2} $ = 0.83 and k = 1.01, respectively. The external validation results also confirm the fitness of the model. The results indicated that, atom-based 3D-QSAR models and further modifications in PDK1 inhibitors via pharmacophore hypothesis are rational for the prediction of the activity of new inhibitors in prospect of drug design. 相似文献
50.
Joji Kurian Thomas Min-Sik Kim Lavanya Balakrishnan Vishalakshi Nanjappa Rajesh Raju Arivusudar Marimuthu Aneesha Radhakrishnan Babylakshmi Muthusamy Aafaque Ahmad Khan Sruthi Sakamuri Shantal Gupta Tankala Mukul Singal Bipin Nair Ravi Sirdeshmukh Aditi Chatterjee T S Keshava Prasad Anirban Maitra Harsha Gowda Ralph H Hruban Akhilesh Pandey 《Cancer biology & therapy》2014,15(8):963-967