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排序方式: 共有654条查询结果,搜索用时 11 毫秒
1.
Tirone E David Tommaso Regesta Gheorghe Gavra Susan Armstrong Manjula D Maganti 《European journal of cardio-thoracic surgery》2007,31(1):43-48
OBJECTIVE: To examine the outcomes of surgery for active infective endocarditis with paravalvular abscess. METHODS: Paravalvular abscess was defined as infective necrosis of the valve annulus that required patch reconstruction before implanting a new valve. Of 383 patients with active infective endocarditis who underwent surgical treatment, 135 (35%) had paravalvular abscess. Patients' mean age was 51+/-16 years and 68% were men. The infected valve was native in 69 patients and prosthetic in 66. The abscess involved the aortic annulus in 73 patients, the mitral annulus in 27, the aortic and mitral annuluses in 33, and the aortic and tricuspid and/or pulmonary annuluses in 2. Surgery consisted of radical resection of the abscess, reconstruction of the annulus with patches and valve replacement. Mean follow-up was 6.2+/-5.2 years and complete. RESULTS: There were 21 (15.5%) operative deaths. Preoperative shock and abscess in the aortic and mitral annuluses were independent predictors of operative death. There were 34 (25%) late deaths. Survival at 15 years was 43+/-6% for all patients, 50+/-8% for native valve endocarditis and 35+/-9% for prosthetic (p=0.41). Age by increments of 5 years and recurrent endocarditis were independent predictors of late death. There were 16 episodes of recurrent endocarditis in 15 patients, and the freedom from recurrent endocarditis was 82+/-4% at 15 years. Fifteen reoperations were performed in 14 patients. Freedom from reoperation was 72+/-9% at 15 years. CONCLUSIONS: Surgery for active endocarditis with paravalvular abscess was associated with high operative mortality, particularly in patients in shock and abscess of both mitral and aortic annuluses. Long-term survival was adversely affected by age and recurrent bouts of endocarditis. 相似文献
2.
Manjula K. Gupta Karen Seifarth Sharad D. Deodhar O. P. Schumacher 《Journal of clinical laboratory analysis》1987,1(1):124-128
A sensitive, simultaneous sandwich enzyme immunoassay for TSH was evaluated especially for its ability to distinguish hyperthyroid patients from the euthyroid population. A total of 140 patient samples was analzyed by this assay as well as with a two-step sandwich radioimmunoassay. The diagnostic sensitivity of the thyrotropin assay was 92.5% and the specificity was 88%. False negatives by thyrotropin assay included two patients with Graves' disease who were being treated with propranolol at the time of testing and one patient who was considered hyperthyroid while receiving synthroid. Twelve patients with elevated free thyroxine index levels were considered euthyroid and 50% of these had thyrotropin values that were undetectable; most were elderly patients with nonthyroidal illnesses. Although the thyrotropin enzyme immunoassay had good sensitivity and precision for the detection of hyperthyroidism, our data suggest the limitation of a single thyrotropin determination in establishing the euthyroid state, especially in elderly patients with associated nonthyroidal illnesses and hyperthyroxinemia. 相似文献
3.
Enhanced molecular volume of conservatively pegylated Hb: (SP-PEG5K)6-HbA is non-hypertensive 总被引:2,自引:0,他引:2
Acharya SA Friedman JM Manjula BN Intaglietta M Tsai AG Winslow RM Malavalli A Vandegriff K Smith PK 《Artificial cells, blood substitutes, and immobilization biotechnology》2005,33(3):239-255
Recent studies have suggested that the "pressor effect" of acellular Hb is a consequence of perturbation of the macro-and microcirculatory system in multiple ways, and that PEGylation is an effective approach for controlling the same. In an attempt to confirm this concept, a new and simple thiolation mediated, maleimide chemistry-based conservative PEGylation protocol has been developed to conjugate multiple copies of PEG-chains to Hb. This approach combines the high reactivity of maleimides towards thiols with the propensity of iminothiolane to derivatize the epsilon-amino groups of proteins into reactive thiol groups, with conservation of their positive charge. One of the PEGylated products, namely (SP-PEG5K)6-HbA, that carries on an average six copies of PEG5000 chains per Hb, is non-hypertensive in hamster top load and in rat 50% exchange transfusion models. This hexa-PEGylated-Hb has (i) a hydrodynamic volume corresponding to that of an oligomerized Hb of 256kDa, (ii) a molecular radius of approximately 6.8 nm, (iii) high oxygen affinity, (iv) lowered Bohr effect, and (v) increased viscosity and colloidal osmotic pressure. These properties of (SP-PEG5K)6-HbA are consistent with the emerging new paradigms for the design of Hb based oxygen carriers and confirm the concept that the "pressor effect" of Hb is a multifactorial event. The thiolation mediated maleimide chemistry-based PEGylation protocol described here for the generation of (SP-PEG5K)6-Hb is simple, highly efficient, and is carried out under oxy conditions. The results demonstrate that a non-hypertensive PEG-Hb can be generated by conjugation of a lower number of PEG chains than previously reported. 相似文献
4.
Tuberculosis, as yet, is far from being controlled. Several reasons can be attributed to this, a major contributing factor being the development of resistance to the currently available drugs due to the successful adaptation of the pathogen. Most of the inferences about the pathogen are based on the observation of mycobacteria grown in synthetic media in vitro and of the mycobacteria maintained in macrophages simulating the in vivo conditions. Molecular studies in mycobacteria had been slow to come due to the difficulty in the generation of mutants. However, new technologies that have now been developed for studying in vivo expressed molecules in other bacterial systems are being successfully applied to mycobacteria, especially the pathogenic M. tuberculosis. Additionally, an equally important factor in the study of the disease is the genetic predisposition of population to the infection. New findings link the Nramp1 and Toll receptor polymorphisms to susceptibility to infectious diseases. 相似文献
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6.
Intravenous delivery of adenovirus-mediated soluble FLT-1 results in liver toxicity. 总被引:3,自引:0,他引:3
Parameshwar J Mahasreshti Manjula Kataram Ming H Wang Cecil R Stockard William E Grizzle Delicia Carey Gene P Siegal Hidde J Haisma Ronald D Alvarez David T Curiel 《Clinical cancer research》2003,9(7):2701-2710
PURPOSE: Vascular endothelial growth factor (VEGF) is a potent angiogenic agent and plays a major role in tumor growth and metastases. We have previously reported the locoregional (i.p.) delivery of adenovirus-mediated antiangiogenic soluble FLT-1 (sFLT-1; a naturally encoded potent VEGF antagonist) gene therapy to inhibit VEGF action in a murine ovarian carcinoma model. This study was predicated on the fact that systemic delivery of sFLT-1 might allow an approach for therapy of disseminated tumor. The purpose of this study is to test the effects of i.v. delivered, adenovirus-mediated sFLT-1 on the survival duration in a murine ovarian tumor model and to evaluate the safety of i.v.-delivered versus i.p.-delivered adenovirus-mediated sFLT-1 in non-tumor-bearing mice. EXPERIMENTAL DESIGN: To determine the effects of i.v.-administered adenovirus-mediated sFLT-1 on survival duration of mice bearing i.p. human ovarian tumors, an E1A/B-deleted, (replication-deficient) infectivity-enhanced recombinant adenovirus AdRGDGFPsFLT-1 encoding cDNA for both sFLT-1 and GFP (green fluorescent protein), a control adenovirus AdRGDGFP encoding GFP alone, or PBS was delivered i.v. The therapeutic effect of sFLT-1 was evaluated by survival duration of the mice. Furthermore, the safety of i.v.- or i.p.-delivered adenovirus-mediated sFLT-1 was evaluated by administering AdRGDGFPsFLT-1, AdRGDGFP, or PBS either i.v. or i.p. into non-tumor-bearing mice. Adenovirus-mediated gene expression was determined by determining GFP expression using fluorescent microscopy and by assessing sFLT-1 expression in liver, lungs, spleen, and kidneys by immunohistochemistry using anti-FLT-1 monoclonal antibody. Systemic levels of sFLT-1 were evaluated by ELISA and the toxicity was evaluated by histopathology. RESULTS: The i.v. delivery of AdRGDGFPsFLT-1 in the ovarian tumor model resulted in a shorter duration of survival of the mice as compared with the control group. Furthermore, in the safety evaluation experiment, i.v. administration of AdRGDGFPsFLT-1 in non-tumor-bearing mice principally localized to the liver. This localization lead to sFLT-1 overexpression, mainly in the liver, resulting in hemorrhage and tissue toxicity. However, i.p. delivery of AdRGDGFPsFLT-1 did not localize principally to the liver, leading to negligible expression of sFLT-1, and no intrahepatic hemorrhage or toxicity was observed. The i.v. delivery of the control virus AdRGDGFP also principally localized to the liver, leading to GFP expression mainly in the liver. However, neither hemorrhage nor morphological cytotoxicity was observed. i.p. delivery of AdRGDGFP resulted in ectopic localization to the liver with very little GFP expression and no toxicity. These results suggest that overexpression of sFLT-1 in the liver as a result of i.v. delivery is hepatotoxic. CONCLUSIONS: Our results suggest that i.v. delivery of the sFLT-1 gene via replication-deficient, infectivity-enhanced recombinant adenoviral vectors will result in overexpression of sFLT-1 in the liver leading to unacceptable hepatotoxicity. Tumor-specific targeting of the vectors and tumor-specific expression strategies should be used to ensure a clinically useful antiangiogenesis gene therapy. 相似文献
7.
Teja Srinivas Nirujogi Sainath R. Kotha Sangwoon Chung Brenda F. Reader Anita Yenigalla Liwen Zhang John P. Shapiro Jon Wisler John W. Christman Krishnarao Maddipati Narasimham L. Parinandi Manjula Karpurapu 《Journal of innate immunity》2022,14(5):555
Emerging data support the pivotal role of extracellular vesicles (EVs) in normal cellular physiology and disease conditions. However, despite their abundance, there is much less information about the lipid mediators carried in EVs, especially in the context of acute lung injury (ALI). Our data demonstrate that C57BL/6 mice subjected to intranasal Escherichia coli lipopolysaccharide (LPS)-induced ALI release, a higher number of EVs into the alveolar space, compared to saline-treated controls. EVs released during ALI originated from alveolar epithelial cells, macrophages, and neutrophils and carry a diverse array of lipid mediators derived from ω-3 and ω-6 polyunsaturated fatty acids (PUFA). The eicosanoids in EVs correlated with cellular levels of arachidonic acid, expression of cytosolic phospholipase A2, cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome epoxygenase p450 proteins in pulmonary macrophages. Furthermore, EVs from LPS-toll-like receptor 4 knockout (TLR4<sup>-/-</sup>) mice contained significantly lower amounts of COX and LOX catalyzed eicosanoids and ω-3 PUFA metabolites. More importantly, EVs from LPS-treated wild-type mice increased TNF-α release by macrophages and reduced alveolar epithelial monolayer barrier integrity compared to EVs from LPS-treated TLR4<sup>−/−</sup> mice. In summary, our study demonstrates for the first time that the EV carried PUFA metabolite profile in part depends on the inflammatory status of the lung macrophages and modulates pulmonary macrophage and alveolar epithelial cell function during LPS-induced ALI. 相似文献
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Rashna Dass Himesh Barman Sourabh Gohain Duwarah Vivek Choudhury Pankaj Jain Nayan Mani Deka Manjula Murari 《Rheumatology international》2010,30(8):1099-1101
Macrophage activation syndrome (MAS) is a clinical syndrome caused by an excessive proliferation of T lymphocytes and well-differentiated
macrophages; an entity distinct from malignant histiocytosis. Although rheumatologic conditions are the common cause of MAS,
a wide range of infections are also seen to cause MAS. We report an adolescent with severe Plasmodium falciparum malaria and MAS. He fulfilled six out of eight criteria required to diagnose hemophagocytic lymphohistiocytosis. 相似文献