全文获取类型
收费全文 | 478篇 |
免费 | 41篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 11篇 |
妇产科学 | 9篇 |
基础医学 | 82篇 |
口腔科学 | 9篇 |
临床医学 | 54篇 |
内科学 | 82篇 |
皮肤病学 | 16篇 |
神经病学 | 11篇 |
特种医学 | 4篇 |
外科学 | 72篇 |
综合类 | 10篇 |
预防医学 | 42篇 |
眼科学 | 1篇 |
药学 | 77篇 |
中国医学 | 5篇 |
肿瘤学 | 32篇 |
出版年
2024年 | 1篇 |
2023年 | 4篇 |
2022年 | 12篇 |
2021年 | 19篇 |
2020年 | 14篇 |
2019年 | 12篇 |
2018年 | 16篇 |
2017年 | 9篇 |
2016年 | 17篇 |
2015年 | 17篇 |
2014年 | 24篇 |
2013年 | 13篇 |
2012年 | 41篇 |
2011年 | 38篇 |
2010年 | 16篇 |
2009年 | 20篇 |
2008年 | 24篇 |
2007年 | 20篇 |
2006年 | 31篇 |
2005年 | 27篇 |
2004年 | 25篇 |
2003年 | 33篇 |
2002年 | 32篇 |
2001年 | 5篇 |
2000年 | 2篇 |
1999年 | 6篇 |
1998年 | 6篇 |
1997年 | 4篇 |
1996年 | 3篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1979年 | 2篇 |
1977年 | 3篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1970年 | 1篇 |
1967年 | 2篇 |
排序方式: 共有520条查询结果,搜索用时 15 毫秒
1.
2.
3.
Stability of Th1 and Th2 populations 总被引:19,自引:0,他引:19
Perez Victor L.; Lederer James A.; Lichtman Andrew H.; Abbas Abul K. 《International immunology》1995,7(5):869-875
Using an in vitro model for the development of IFN-y-producIng(Th1) and IL-4-produclng (Th1) cells from CD4 T lymphocytesexpressing a transgenlc TCR, we show that IL-12 and IL-4 arethe most potent stimuli for the differentiation of naive T cellsto effector populations. When combinations of cytokines arepresent during T cell priming, the effect of IL-4 Is dominant.Furthermore, differentiated Th1 cells can be converted intoIL-4 producers by exposure to IL-4, but the Th2 phenotype Isnot reversible. The stability of Th2 populations may limit theability to regulate Th2-domlnant responses In pathologic situations. 相似文献
4.
M. Alauddin Abul Hasnat Joarder 《Indian journal of otolaryngology and head and neck surgery》2004,56(3):201-205
All patients (n=154) of thyroid malignancy admitted in the Otoluryngology Department of Bangabandhu Sheikh Mujib Medical University (former IPGMR) between 1986 and 2000 were retrospectively analyzed to find out the extent and result of surgery used for thyroid carcinoma. The other objectives were to find out the incidence of differentiated thyroid carcinoma among the thyroid malignancy and also to find out the age, sex and clinical presentation of papillary and follicular carcinoma. Among all the thyroid malignancy (n-154), Differentiated Thyroid Carcinoma (DTC) was seen in 130 (84.41%) cases, where as papillary carcinoma occurred in 98(63.64%), and follicular carcinoma in 32(20.77%)cases. On the basis of risk factors, the DTC were designated as low and high risk. The year-wise incidence of DTC revealed increasing trend from 1986 (3 cases) to 2000 (23 cases). Among the 98 papillary thyroid carcinoma highest number of cases (35.71%) were seen in 31-40 year age group. The male to female ratio was 1: 1.64. In follicular carcinoma, highest number (35.25%) of cases were also seen in 31-40 year age group. The male to female ratio was 1:1.66. The commonest presentation in papillary carcinoma was thyroid swelling (96.93%). The other presentations were occult thyroid (3.06%), Cervical lymph node metastasis (38.77%) and distant metastasis (2.04%). In Follicular carcinoma, the presentations were thyroid swelling (100%), Cervical lymph node metastasis (6.25%) and Distant metastasis (21.87%). In this series, low risk DTC were treated by Lobectomy & Isthmusectomy plus Thyroxin. In low risk group the rate of recurrence was 6.89% and the mortality was nil in five years follow-up. Except two inoperable cases, all high risk patients were managed by Total thyroidectomy (with or without neck dissection, plus removal of metastatic lesion when required) with Radioiodine ablation plus Thyroxin. . The rate of recurrence was 7.81% and mortality was 1.56% in high risk group in similar period of time. Vocal cord palsy were noted in 5 (3.84%) unilateral, and inane (0.76%) bilateral cases. Hypoparathyroidism was found in 4.61%. 相似文献
5.
Abul Mokarim Masataka Uetani Ichiro Sakamoto Nobuyuki Hayashi Koichiro Nomata Hiroshi Ohtani 《Acta oncologica (Stockholm, Sweden)》1997,36(2):175-181
Forty-five patients (median age 63 years) with muscle invasive bladder cancer were treated with transcatheter intraarterial infusion (TAI) of cisplatin (CDDP) and doxorubicin. They received a total of 114 courses (median 3 courses per patient) of TAI. Complete response was obtained in 20 patients (44%), partial response in 17 (38%), stable disease in 6(13%), and progression of disease in 2 patients (5%). The overall response rate was 82% at a median follow-up of 36 months. The actuarial survival of the patient population was 72% at 5 years; 36 patients were alive and 9 had died of cancer progression. The treatment was generally extremely well tolerated without major complications. The current study also revealed the fact that papillary carcinomas were more sensitive to this therapy than were non-papillary tumors. Overall, response rate and local control were significantly higher in low-grade than in high-grade tumors. The observed high complete response and good survival rate suggest that intraarterial CDDP and doxorubicin might be highly effective for localized invasive bladder cancer. 相似文献
6.
Ibrahim A. Aljuffali Mohd. Abul Kalam Yasmin Sultana Ahamad Imran Aws Alshamsan 《Saudi Pharmaceutical Journal》2015,23(1):85-94
Quantitative determination of gatifloxacin in tablets, solid lipid nanoparticles (SLNs) and eye-drops using a very simple and rapid chromatographic technique was validated and developed. Formulations were analyzed using a reverse phase SUPELCO® 516 C-18-DB, 50306-U, HPLC column (250 mm × 4.6 mm, 5 μm) and a mobile phase consisting of disodium hydrogen phosphate buffer:acetonitrile (75:25, v/v) and with orthophosphoric acid pH was adjusted to 3.3 The flow rate was 1.0 mL/min and analyte concentrations were measured using a UV-detector at 293 nm. The analyses were performed at room temperature (25 ± 2 °C). Gatifloxacin was separated in all the formulations within 2.767 min. There were linear calibration curves over a concentration range of 4.0–40 μg.mL−1 and correlation coefficients of 0.9998 with an average recovery above 99.91%. Detection of analyte from different dosage forms at the same Rt indicates the specificity and stability of the developed method. 相似文献
7.
Renáta Váraljai Abul B.M.M.K. Islam Michael L. Beshiri Jalees Rehman Nuria Lopez-Bigas Elizaveta V. Benevolenskaya 《Genes & development》2015,29(17):1817-1834
The retinoblastoma tumor suppressor protein pRb restricts cell growth through inhibition of cell cycle progression. Increasing evidence suggests that pRb also promotes differentiation, but the mechanisms are poorly understood, and the key question remains as to how differentiation in tumor cells can be enhanced in order to diminish their aggressive potential. Previously, we identified the histone demethylase KDM5A (lysine [K]-specific demethylase 5A), which demethylates histone H3 on Lys4 (H3K4), as a pRB-interacting protein counteracting pRB''s role in promoting differentiation. Here we show that loss of Kdm5a restores differentiation through increasing mitochondrial respiration. This metabolic effect is both necessary and sufficient to induce the expression of a network of cell type-specific signaling and structural genes. Importantly, the regulatory functions of pRB in the cell cycle and differentiation are distinct because although restoring differentiation requires intact mitochondrial function, it does not necessitate cell cycle exit. Cells lacking Rb1 exhibit defective mitochondria and decreased oxygen consumption. Kdm5a is a direct repressor of metabolic regulatory genes, thus explaining the compensatory role of Kdm5a deletion in restoring mitochondrial function and differentiation. Significantly, activation of mitochondrial function by the mitochondrial biogenesis regulator Pgc-1α (peroxisome proliferator-activated receptor γ-coactivator 1α; also called PPARGC1A) a coactivator of the Kdm5a target genes, is sufficient to override the differentiation block. Overexpression of Pgc-1α, like KDM5A deletion, inhibits cell growth in RB-negative human cancer cell lines. The rescue of differentiation by loss of KDM5A or by activation of mitochondrial biogenesis reveals the switch to oxidative phosphorylation as an essential step in restoring differentiation and a less aggressive cancer phenotype. 相似文献
8.
Ahmad Almilaji Carlos Munoz Bernat Elvira Abul Fajol Tatsiana Pakladok Sabina Honisch Ekaterina Shumilina Florian Lang Michael Föller 《Pflügers Archiv : European journal of physiology》2013,465(11):1573-1582
Besides their role in cardiac repolarization, human ether-a-go-go-related gene potassium (hERG) channels are expressed in several tumor cells including rhabdomyosarcoma cells. The channels foster cell proliferation. Ubiquitously expressed AMP-dependent protein kinase (AMPK) is a serine-/threonine kinase, stimulating energy-generating and inhibiting energy-consuming processes thereby helping cells survive periods of energy depletion. AMPK has previously been shown to regulate Na+/K+ ATPase, Na+/Ca2+ exchangers, Ca2+ channels and K+ channels. The present study tested whether AMPK regulates hERG channel activity. Wild type AMPK (α1β1γ1), constitutively active γR70QAMPK (α1β1γ1(R70Q)), or catalytically inactive αK45RAMPK (α1(K45R)β1γ1) were expressed in Xenopus oocytes with hERG. Tail currents were determined as a measure of hERG channel activity by two-electrode-voltage clamp. hERG membrane abundance was quantified by chemiluminescence and visualized by immunocytochemistry and confocal microscopy. Moreover, hERG currents were measured in RD rhabdomyosarcoma cells after pharmacological modification of AMPK activity using the patch clamp technique. Coexpression of wild-type AMPK and of constitutively active γR70QAMPK significantly downregulated the tail currents in hERG-expressing Xenopus oocytes. Pharmacological activation of AMPK with AICAR or with phenformin inhibited hERG currents in Xenopus oocytes, an effect abrogated by AMPK inhibitor compound C. γR70QAMPK enhanced the Nedd4-2-dependent downregulation of hERG currents. Coexpression of constitutively active γR70QAMPK decreased membrane expression of hERG in Xenopus oocytes. Compound C significantly enhanced whereas AICAR tended to inhibit hERG currents in RD rhabdomyosarcoma cells. AMPK is a powerful regulator of hERG-mediated currents in both, Xenopus oocytes and RD rhabdomyosarcoma cells. AMPK-dependent regulation of hERG may be particularly relevant in cardiac hypertrophy and tumor growth. 相似文献
9.
Johirul Islam Alpa Shree Shekh M. Afzal Abul Vafa Sarwat Sultana 《Environmental toxicology》2020,35(7):747-757
Diosmin, a naturally occurring flavonoid commonly present in citrus fruit, is known to exhibit anti‐inflammatory, antimutagenic, antioxidant, and free radical scavenging as well as blood lipid lowering activities among others. Diosmin has also been used for the treatment of various diseases including diabetes mellitus and Alzheimer's disease. Our study explores the role of Diosmin in pulmonary toxicity (lung injury) induced by environmental contaminant benzo(a)pyrene [B(a)P]. Swiss Albino Mice (SAM) were administered with either Diosmin 100 or 200 mg/kg body weight daily for 14 days and then challenged with a single dose of B(a)P. On the 15th day, animals were sacrificed; lung tissues and blood were collected for molecular analysis. B(a)P administration in mice induced the thickening of lung epithelium, damaged alveolar architecture, and promoted inflammatory cell infiltration in the lung tissues. Also, B[a]P significantly increased the expression of NF‐kB, COX‐2, IL‐6, Bax, cleaved caspase 3, and cleaved PARP proteins and decreased antioxidant enzyme levels. Diosmin‐100 and Diosmin‐200 significantly attenuated the damage to lung epithelium, alveolar architecture, and reduced inflammatory cell infiltration in the lung tissues of mice. Diosmin significantly (P < .05) attenuated the levels of oxidative stress markers: lactate dehydrogenase and xanthine oxidase. A decrease in expression of NF‐kB, COX‐2, IL‐6, Bax, cleaved caspase 3, and cleaved PARP proteins in mice was challenged with B[a]P. Diosmin thus could be a promising therapeutic adjuvant against B[a]P‐induced oxidative stress and lung damage. 相似文献
10.