全文获取类型
收费全文 | 2539篇 |
免费 | 124篇 |
国内免费 | 8篇 |
专业分类
耳鼻咽喉 | 21篇 |
儿科学 | 469篇 |
妇产科学 | 41篇 |
基础医学 | 254篇 |
口腔科学 | 23篇 |
临床医学 | 154篇 |
内科学 | 501篇 |
皮肤病学 | 57篇 |
神经病学 | 116篇 |
特种医学 | 66篇 |
外科学 | 435篇 |
综合类 | 57篇 |
一般理论 | 2篇 |
预防医学 | 97篇 |
眼科学 | 45篇 |
药学 | 153篇 |
中国医学 | 6篇 |
肿瘤学 | 174篇 |
出版年
2023年 | 19篇 |
2022年 | 20篇 |
2021年 | 45篇 |
2020年 | 30篇 |
2019年 | 37篇 |
2018年 | 75篇 |
2017年 | 39篇 |
2016年 | 70篇 |
2015年 | 54篇 |
2014年 | 84篇 |
2013年 | 105篇 |
2012年 | 178篇 |
2011年 | 162篇 |
2010年 | 114篇 |
2009年 | 71篇 |
2008年 | 128篇 |
2007年 | 123篇 |
2006年 | 110篇 |
2005年 | 101篇 |
2004年 | 79篇 |
2003年 | 101篇 |
2002年 | 97篇 |
2001年 | 83篇 |
2000年 | 79篇 |
1999年 | 62篇 |
1998年 | 29篇 |
1997年 | 15篇 |
1996年 | 20篇 |
1995年 | 15篇 |
1994年 | 21篇 |
1993年 | 9篇 |
1992年 | 48篇 |
1991年 | 51篇 |
1990年 | 32篇 |
1989年 | 29篇 |
1988年 | 26篇 |
1987年 | 28篇 |
1986年 | 28篇 |
1985年 | 30篇 |
1984年 | 19篇 |
1983年 | 13篇 |
1981年 | 21篇 |
1979年 | 15篇 |
1978年 | 16篇 |
1977年 | 25篇 |
1976年 | 26篇 |
1975年 | 10篇 |
1974年 | 11篇 |
1973年 | 8篇 |
1968年 | 8篇 |
排序方式: 共有2671条查询结果,搜索用时 0 毫秒
61.
Christian Tomuschat Anne Marie O’Donnell David Coyle Prem Puri 《Pediatric surgery international》2016,32(12):1201-1207
Purpose
Hirschsprung’s disease-associated enterocolitis (HAEC) is the most common cause of morbidity and mortality in Hirschsprung’s disease (HSCR). Altered intestinal epithelial barrier function is implicated in the pathogenesis of HAEC. IL-17 is a proinflammatory cytokine that plays a crucial role in host defense against microbial organisms in the development of inflammatory diseases. Act1 is an essential adaptor molecule required for the IL-17-mediated inflammatory responses via interaction with IL-17 receptor (IL-17R). We designed this study to investigate the hypothesis that Act1/Il-17R expression is upregulated in HSCR.Methods
We investigated Act1 and IL17R expression in ganglionic andaganglionic bowel of HD patients (n = 10) and controls (n = 10). qPCR, Western blotting and confocal immunofluorescence were performed.Main results
qPCR and Western blot analysis revealed that Act1 and IL17R are strongly expressed in the aganglionic and ganglionic colon of patients with HSCR. Act1 and IL17R expression was significantly increased in HSCR specimens compared to controls (p < 0.05). Confocal microscopy revealed a markedly increased expression of Act1 and IL17R in the colonic epithelium of patients with HSCR compared to controls.Conclusion
To our knowledge, we report, for the first time, the expression of Act1 in the human colon. The increased expression of Act1 and Il-17 in the aganglionic and ganglionic bowel in HSCR may result in IL-17-mediated increased inflammatory response leading to the development of HAEC62.
63.
64.
Toshiaki Takahashi Florian Friedmacher Julia Zimmer Prem Puri 《Pediatric surgery international》2016,32(2):135-140
Purpose
Developmental mutations that inhibit normal formation of extracellular matrix (ECM) in fetal diaphragms have been identified in congenital diaphragmatic hernia (CDH). FRAS1 and FRAS1-related extracellular matrix 2 (FREM2), which encode important ECM proteins, are secreted by mesenchymal cells during diaphragmatic development. The FRAS1/FREM2 gene unit has been shown to form a ternary complex with FREM1, which plays a crucial role during formation of human and rodent diaphragms. Furthermore, it has been demonstrated that the diaphragmatic expression of FREM1 is decreased in the nitrofen-induced CDH model. We hypothesized that FRAS1 and FREM2 expression is decreased in the developing diaphragms of fetal rats with nitrofen-induced CDH.Methods
Pregnant rats were exposed to either nitrofen or vehicle on gestational day 9 (D9), and fetuses were harvested on D13, D15 and D18. Microdissected diaphragms were divided into nitrofen-exposed/CDH and control samples (n = 12 per time-point and experimental group, respectively). Diaphragmatic gene expression levels of FRAS1 and FREM2 were analyzed by qRT-PCR. Immunofluorescence double staining for FRAS1 and FREM2 was combined with the mesenchymal marker GATA4 in order to evaluate protein expression and localization in pleuroperitoneal folds (PPFs) and fetal diaphragmatic tissue.Results
Relative mRNA expression of FRAS1 and FREM2 were significantly reduced in PPFs of nitrofen-exposed fetuses on D13 (1.76 ± 0.86 vs. 3.09 ± 1.15; p < 0.05 and 0.47 ± 0.26 vs. 0.82 ± 0.36; p < 0.05), developing diaphragms of nitrofen-exposed fetuses on D15 (1.45 ± 0.80 vs. 2.63 ± 0.84; p < 0.05 and 0.41 ± 0.16 vs. 1.02 ± 0.49; p < 0.05) and fully muscularized diaphragms of CDH fetuses on D18 (1.35 ± 0.75 vs. 2.32 ± 0.92; p < 0.05 and 0.37 ± 0.24 vs. 0.70 ± 0.32; p < 0.05) compared to controls. Confocal laser scanning microscopy revealed markedly diminished FRAS1 and FREM2 immunofluorescence in diaphragmatic mesenchyme, which was associated with reduced proliferation of mesenchymal cells in nitrofen-exposed PPFs and fetal CDH diaphragms on D13, D15 and D18 compared to controls.Conclusion
Decreased mesenchymal expression of FRAS1 and FREM2 in the nitrofen-induced CDH model may cause failure of the FRAS1/FREM2 gene unit to activate FREM1 signaling, disturbing the formation of diaphragmatic ECM and thus contributing to the development of diaphragmatic defects in CDH.65.
66.
Kumar A Kumar K Korde R Puri SK Malhotra P Singh Chauhan V 《Infection and immunity》2007,75(4):2026-2034
Cysteine proteases (falcipains) of Plasmodium falciparum are potential targets for antimalarial chemotherapy, since they have been shown to be involved in important cellular functions such as hemoglobin degradation and invasion/rupture of red blood cells during parasite life cycle. The role of falcipain-1 at the asexual blood stages of the parasite still remains uncertain. This is mainly due to a lack of methods to prepare this protein in an active form. In order to obtain biologically active falcipain-1, a number of falcipain-1 constructs were designed and a systematic assessment of the refolding conditions was done. We describe here the expression, purification, and characterization of a falcipain-1 construct encoding mature falcipain-1 and 35 amino acids from the C-terminal of the pro domain. Recombinant falcipain-1 was overexpressed in the form of inclusion bodies, solubilized, and purified by Ni2+-nitrilotriacetic acid affinity chromatography under denaturing conditions. A systemic approach was then followed to optimize refolding parameters. An optimum refolding condition was obtained, and the yield of the purified refolded falcipain-1 was ~1 mg/liter. Activity of the protein was analyzed by fluorometric and gelatin degradation assays. Immunolocalization studies using anti-falcipain-1 sera revealed a distinct staining at the apical end of the P. falciparum merozoites. Previous studies using falcipain-1-specific inhibitors have suggested a role of falcipain-1 in merozoite invasion. Based on its localization and its role in invasion, we analyzed the immunogenicity of falcipain-1 in mice, followed by heterologous challenge with Plasmodium yoelii sporozoites. Our results suggest a possible role of falcipain-1 in merozoite invasion. 相似文献
67.
The study was undertaken to determine the accuracy of cytological diagnosis of CNS lesions by comparing it with the final histopathological diagnosis of CT guided stereotactic brain biopsy. Squash preparations were prepared from 25 cases of CNS lesions operated in two years. These included 18 astrocytomas, 1 metastatic deposits, 1 epidermoid cyst, 1 Toxoplasmosis, 1 granulomatous inflammation and 3 cases showing normal brain parenchyma. The cytological diagnosis was available to the neurosurgeon within 10 minutes. The cytohistological correlation with paraffin block sections worked out to be 92%. Thus, this proved to be a fairly reliable and rapid method for immediate intra-operative diagnosis. 相似文献
68.
Vibha Puri David Brancazio Eranda Harinath Alexander R. Martinez Parind M. Desai Keith D. Jensen Jung-Hoon Chun Richard D. Braatz Allan S. Myerson Bernhardt L. Trout 《International journal of pharmaceutics》2018,535(1-2):106-112
We demonstrate the coating of tablets using an injection molding (IM) process that has advantage of being solvent free and can provide precision coat features. The selected core tablets comprising 10% w/w griseofulvin were prepared by an integrated hot melt extrusion-injection molding (HME-IM) process. Coating trials were conducted on a vertical injection mold machine. Polyethylene glycol and polyethylene oxide based hot melt extruded coat compositions were used. Tablet coating process feasibility was successfully demonstrated using different coating mold designs (with both overlapping and non-overlapping coatings at the weld) and coat thicknesses of 150 and 300?μm. The resultant coated tablets had acceptable appearance, seal at the weld, and immediate drug release profile (with an acceptable lag time). Since IM is a continuous process, this study opens opportunities to develop HME-IM continuous processes for transforming powder to coated tablets. 相似文献
69.
Aniket A. Kawatkar Joel W. Hay William Stohl Michael B. Nichol 《Health services & outcomes research methodology》2018,18(2):75-95
We estimate multiple treatment effects in presence of selection-bias and response heterogeneity, using panel data. A control function was added to a fixed-effects based correlated random coefficients model. Selection model to create the control function was contrasted between multinomial logit and multinomial probit. For the multinomial logit model, parametric and semi-parametric bias correction techniques, as proposed in Lee (Econometrica 51(2):507–512, 1983), Dubin and McFadden (Econometrica 52(2):345–362, 1984) and Dahl (Econometrica 70(6):2367–2420, 2002) respectively, were implemented. We find that controlling time-varying endogeneity, allowing response heterogeneity, the type of bias correction method and the choice of the selection model, each had significant impact on the estimated treatment effects. Using the case of biologic DMARDs, we show that in the presence of heterogeneity and multiple treatments, the specification of the latent index model should be carefully chosen along with selection bias correction techniques appropriate to the choice of the latent index model. These issues have an important impact on policy. Under one set of assumptions, we may accept a formulary expansion policy on biologic DMARDs to be cost-neutral, while rejecting the same policy as not cost-saving under another set of assumptions. 相似文献
70.
In this double blind randomised placebo controlled study, we investigated the antianginal efficacy of oral captopril in 33 patients of angiographically documented coronary artery disease (chronic stable angina). Apart from sublingual nitrates, all other antianginal drugs were withdrawn. Patients were then evaluated both subjectively by questionnaire and objectively by treadmill stress test. No patient had more than mild hypertension and all patients had good left ventricular function. One group of patients received oral captopril while the other group was given placebo. A repeat assessment was done after six weeks and the results compared with baseline. Anginal attacks decreased from 20.11 +/- 1.86 per week on placebo to 9.92 +/- 1.38 (p < 0.01) on captopril as also the number of sublingual nitrates (18.84 +/- 3.01 to 11.14 +/- 2.94, p < 0.01). Assessment by the treadmill stress test showed that in comparison to the pretreatment test, captopril therapy resulted in a significantly increased exercise duration (6.26 +/- 0.21 to 6.98 +/- 0.31 minutes, p < 0.05), total work done (6.76 +/- 0.26 METS to 7.48 +/- 0.29 METS, p < 0.05). In addition there was a significant increase in time to angina (6.16 +/- 0.18 to 6.85 +/- 0.24 min, p < 0.05) and time to 1mm ST depression (5.18 +/- 0.26 to 6.46 +/- 0.30 min, p < 0.01). We conclude that captopril is an effective monotherapy for patients with chronic stable angina and has both antianginal as well as anti-ischemic effects, possibly secondary to direct coronary vasodilation. 相似文献