全文获取类型
收费全文 | 1570篇 |
免费 | 78篇 |
国内免费 | 20篇 |
专业分类
耳鼻咽喉 | 15篇 |
儿科学 | 54篇 |
妇产科学 | 20篇 |
基础医学 | 210篇 |
口腔科学 | 38篇 |
临床医学 | 114篇 |
内科学 | 391篇 |
皮肤病学 | 16篇 |
神经病学 | 166篇 |
特种医学 | 181篇 |
外科学 | 201篇 |
综合类 | 15篇 |
预防医学 | 52篇 |
眼科学 | 6篇 |
药学 | 110篇 |
肿瘤学 | 79篇 |
出版年
2022年 | 14篇 |
2021年 | 21篇 |
2019年 | 11篇 |
2018年 | 27篇 |
2017年 | 12篇 |
2016年 | 20篇 |
2015年 | 35篇 |
2014年 | 42篇 |
2013年 | 50篇 |
2012年 | 54篇 |
2011年 | 55篇 |
2010年 | 35篇 |
2009年 | 44篇 |
2008年 | 54篇 |
2007年 | 62篇 |
2006年 | 53篇 |
2005年 | 52篇 |
2004年 | 52篇 |
2003年 | 37篇 |
2002年 | 50篇 |
2001年 | 49篇 |
2000年 | 49篇 |
1999年 | 43篇 |
1998年 | 32篇 |
1997年 | 41篇 |
1996年 | 42篇 |
1995年 | 25篇 |
1994年 | 22篇 |
1993年 | 15篇 |
1992年 | 40篇 |
1991年 | 48篇 |
1990年 | 40篇 |
1989年 | 36篇 |
1988年 | 27篇 |
1987年 | 32篇 |
1986年 | 24篇 |
1985年 | 30篇 |
1984年 | 25篇 |
1983年 | 33篇 |
1982年 | 30篇 |
1981年 | 20篇 |
1980年 | 17篇 |
1979年 | 17篇 |
1978年 | 15篇 |
1977年 | 19篇 |
1976年 | 15篇 |
1975年 | 9篇 |
1973年 | 13篇 |
1970年 | 10篇 |
1966年 | 9篇 |
排序方式: 共有1668条查询结果,搜索用时 31 毫秒
81.
Z. M. Novakovic M. C. Leinung D. W. Lee P. Grasso 《Diabetes, obesity & metabolism》2010,12(6):532-539
Background: We have recently shown that intranasal administration of mouse [d ‐Leu‐4]‐OB3 reconstituted in Intravail® to male Swiss Webster mice resulted in significantly higher bioavailability than commonly used injections methods of delivery. The absorption profile associated with intranasal delivery of mouse [d ‐Leu‐4]‐OB3 showed an early peak representing absorption across the nasal mucosa, and a later peak suggesting a gastrointestinal site of uptake. Aim and Methods: In the present study, we examined the effects of orally administered (by gavage) mouse [d ‐Leu‐4]‐OB3 on energy balance, glycaemic control and serum osteocalcin levels in male C57BL/6J wild‐type and ob/ob mice allowed food and water ad libitum or calorie restricted by 40% of normal intake. Results: In wild‐type mice fed ad libitum, oral delivery of mouse [d ‐Leu‐4]‐OB3 reduced body weight gain, food intake and serum glucose, by 4.4, 6.8 and 28.2% respectively. Serum osteocalcin levels and water intake were essentially the same in control and treated wild‐type mice. In ob/ob mice fed ad libitum, mouse [d ‐Leu‐4]‐OB3 reduced body weight gain, food intake, water intake and serum glucose by 11.6, 16.5, 22.4 and 24.4% respectively. Serum osteocalcin in ob/ob mice treated with mouse [d ‐Leu‐4]‐OB3 was elevated by 62% over controls. Calorie restriction alone caused significant weight loss in both wild‐type (9.0%) and ob/ob (4.8%) mice, and mouse [d ‐Leu‐4]‐OB3 did not further enhance this weight loss. As expected, serum glucose levels in wild‐type and ob/ob mice were significantly reduced by calorie restriction alone. Mouse [d ‐Leu‐4]‐OB3 further reduced serum glucose in wild‐type mice and normalized levels in ob/ob mice. Calorie restriction alone reduced serum osteocalcin levels by 44.2% in wild‐type mice and by 19.1% in ob/ob mice. Mouse [d ‐Leu‐4]‐OB3 prevented this decrease in groups of mice. Conclusions: The results of this study suggest that oral delivery of mouse [d ‐Leu‐4]‐OB3 in Intravail® is possible and may have potential not only as an alternative therapy in the treatment of human obesity and some of its associated metabolic dysfunctions, but also may help to prevent and/or reverse at least some of the bone loss which accompanies osteoporosis, anorexia nervosa and other wasting diseases. 相似文献
82.
83.
Micale N Zappalà M Grasso S Puja G De Sarro G Ferreri G De Sarro A Toma L De Micheli C 《Journal of medicinal chemistry》2002,45(20):4433-4442
In this paper we describe the synthesis of a series of novel 2-[(4-alkylsemicarbazono)-(4-aminophenyl)-methyl]-4,5-methylenedioxyphenylacetic acid alkyl esters (10-19) carrying an alkylsemicarbazono moiety at a benzylic site. The influence of this group on the biological activity was evaluated by testing the corresponding derivatives 20-22 in which the 4-alkylsemicarbazono moiety was removed (compound 20) or its alkylureido portion shifted at position 1 (compounds 21-22). Furthermore, the involvement of the 4-aminobenzyl moiety in the anticonvulsant activity was evaluated by testing derivative 23. The anticonvulsant activity of all compounds was assayed against audiogenic seizures induced in DBA/2 mice. Within this series of derivatives, 2-[(4-aminophenyl)-(4-methylsemicarbazono)-methyl]-4,5-methylenedioxyphenylacetic acid methyl ester (10) proved to be the most active compound. It displayed a potency 5-fold higher than that shown by 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (1, GYKI 52466), a well-known noncompetitive 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptor antagonist. Compound 10 was also effective in suppressing seizures induced in Swiss mice by maximal electroshock (MES) or pentylenetetrazole (PTZ). Furthermore, it antagonized in vivo seizures induced by icv administration of AMPA or kainate (KA). Using the patch-clamp technique in primary cultures of granule neurons we tested compounds 10 and 21 for their ability to modulate currents evoked by KA and 2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propionic acid (ATPA). These two derivatives reduced KA and ATPA currents to a larger extent than that shown by reference compound 1. Compounds 10 and 21 were also able to reduce neuronal cell death induced by the application of KA (100 microM). 相似文献
84.
Preferential megalin-mediated transcytosis of low-hormonogenic thyroglobulin: a control mechanism for thyroid hormone release
下载免费PDF全文
![点击此处可从《Proceedings of the National Academy of Sciences of the United States of America》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Lisi S Pinchera A McCluskey RT Willnow TE Refetoff S Marcocci C Vitti P Menconi F Grasso L Luchetti F Collins AB Marino M 《Proceedings of the National Academy of Sciences of the United States of America》2003,100(25):14858-14863
Hormone secretion by thyrocytes occurs by fluid phase uptake and lysosomal degradation of the prohormone thyroglobulin (Tg). However, some Tg internalized by megalin bypasses lysosomes and is transcytosed across cells and released into the bloodstream. Because the hormone content of Tg is variable, we investigated whether this affects transcytosis. We found that rat Tg with a low hormone content [low-hormonogenic rat Tg (low-horm-rTg)] is transcytosed by megalin across thyroid FRTL-5 cells to a greater extent than rat Tg with a high hormone content [hormonogenic rat Tg (horm-rTg)]. In immunoprecipitation experiments, the Tg sequence Arg-2489-Lys-2503 (required for binding to megalin and heparan sulfate proteoglycans) was found to be more exposed in low-horm-rTg, which accounted for its preferential transcytosis. Thus, removal of surface heparan sulfate proteoglycans from FRTL-5 cells or blocking of 2489-2503 reduced transcytosis of low-horm-rTg to a greater extent than that of horm-rTg. Preferential transcytosis of low-horm-rTg affected hormone release. Thus, the increase in hormone release from horm-rTg in FRTL-5 cells determined by megalin blocking (due to reduced transcytosis and enhanced Tg degradation) was rescued by low-horm-rTg, suggesting that megalin is required for effective hormone release. This finding was confirmed in a small number of megalin-deficient mice, which had serological features resembling mild hypothyroidism. Reduced hormone formation within Tg in vivo, due to treatment of rats with aminotriazole or of patients with Graves' disease with methimazole, resulted in increased Tg transcytosis via megalin, in confirmation of results with FRTL-5 cells. Our study points to a major role of megalin in thyroid homeostasis with possible implications in thyroid diseases. 相似文献
85.
Casati V Sandrelli L Speziali G Calori G Grasso MA Spagnolo S 《The Journal of thoracic and cardiovascular surgery》2002,123(6):1084-1091
OBJECTIVE: We studied the hemostatic effects of tranexamic acid in patients undergoing elective surgery involving the thoracic aorta. METHODS: In a double-blind, randomized fashion, 60 consecutive patients were assigned to two treatment groups: 30 patients (placebo group) received infusion of saline solution, and 30 (treatment group) received tranexamic acid (1 g before skin incision, an infusion of 400 mg/h during the operation, and 500 mg in the pump priming). Perioperative bleeding was considered as a primary outcome. Perioperative allogeneic transfusions, major thrombotic complications (myocardial infarction, pulmonary embolism, renal insufficiency), and surgical outcomes were also considered. RESULTS: Patients treated with tranexamic acid showed significant reductions in postoperative bleeding, both in terms of the amount collected during the first 4 postoperative hours (median 307 mL, interquartile range 253-361 mL in the placebo group vs median 211 mL, interquartile range 108-252 mL in the treatment group, P =.002) and in terms of total bleeding (median 722 mL, interquartile range 574-952 mL in the placebo group vs median 411 mL, interquartile range 313-804 mL in the treatment group, P =.04). Consequently, the number of patients transfused differed significantly between groups (21 patients [72.4%] in the placebo group vs 13 [44.8%] in the treatment group, P =.033). Patients in the treatment group showed significant reductions in the total amount for the entire group of packed red cells transfused (13,500 mL in the treatment group vs 28,000 mL in the placebo group, P =.012) and in the total amount of allogeneic transfusions (23,400 mL in the treatment group vs 53,000 mL in the placebo group, P =.024). No differences in perioperative thrombotic complications were found. CONCLUSIONS: In this initial series of patients undergoing thoracic aortic surgery, tranexamic acid appeared effective in reducing perioperative bleeding, with a significant reduction in the need for allogeneic transfusions and without any increased risk of thrombotic complications. 相似文献
86.
Casati V Speziali G D'Alessandro C Cianchi C Antonietta Grasso M Spagnolo S Sandrelli L 《Anesthesiology》2002,97(2):367-373
BACKGROUND: Recently, various studies have questioned the efficacy of intraoperative acute normovolemic hemodilution (ANH) in reducing bleeding and the need for allogeneic transfusions in cardiac surgery. The aim of the present study was to reevaluate the effects of a low-volume ANH in elective, adult open-heart surgery. METHODS: Two hundred four consecutive adult patients undergoing cardiac surgery were prospectively randomized in a nonblinded manner into two groups: ANH group (103 patients), where 5-8 ml/kg of blood was withdrawn before systemic heparinization and replaced with colloid solutions, and a control group, where no hemodilution was performed (101 patients). Procedures included single and multiple valve surgery, aortic root surgery, coronary surgery combined with valve surgery, or partial left ventriculectomy. The purpose of the study was to evaluate the efficacy of ANH in reducing the need for allogeneic blood components. Routine hematochemical evaluations, perioperative blood loss, major complications, and outcomes were also recorded. RESULTS: No differences were found between the groups regarding demographics, baseline hematochemical data, and operative characteristics. There was no difference in the amount of transfusions of packed red cells, fresh frozen plasma, platelet concentrates, total number of patients transfused (control group, 36% vs. ANH group, 34.3%; P = 0.88), and amount of postoperative bleeding (control group, 412 ml [313-552 ml] vs. ANH group, 374 ml [255-704 ml]) (median [25th-75th percentiles]); P = 0.94. Further, perioperative complications, postoperative hematochemical data, and outcomes were not different. CONCLUSIONS: In patients undergoing elective open-heart surgery, low-volume ANH showed lack of efficacy in reducing the need for allogeneic transfusions and postoperative bleeding. 相似文献
87.
Are there general rules for the generation of curvilinear motion of the end-effector? Form and kinematics of the arm trajectory are typically inter-related. A relationship between velocity and curvature of the endpoint path has been previously described and quantified as the two-thirds power law. Here we show that the two-thirds power law holds also for the foot trajectory (during the swing phase) in human locomotion for a wide range of walking speeds and gravitational loads, but air-stepping. In air-stepping, it was violated systematically. The results suggest that the power law represents a general constrain of biological motion, may be attributed to both mechanical and neural factors and can depend on natural interactions with external environment. 相似文献
88.
Nine peritoneovenous shunts were positioned by percutaneous technique in seven patients with advanced malignancy causing severe refractory ascites, and in two patients with hepatic cirrhosis (one with hepatocarcinoma). In all patients the shunts were percutaneously placed through the subclavian vein in the angiographic suite under digital fluoroscopic guide. No complications directly related to the procedure occurred. The shunt was successfully positioned in all patients in 60 min average time. No patient showed symptoms related to pulmonary overload or to disseminated intravascular coagulation. All patients had a significant improvement of the objective symptoms related to ascites such as respiratory symptoms, dyspepsia, and functional impairment to evacuation describing an improvement of their quality of life. Maximum shunt patency was 273 days. Percutaneous placement of peritoneovenous shunt is a safe, fast, and inexpensive procedure, extremely useful in resolution of refractory ascites, reducing symptoms, and allowing effective palliation, with a great improvement in quality of life. 相似文献
89.
Demyelinating plaques in relapsing-remitting and secondary-progressive multiple sclerosis: assessment with diffusion MR imaging 总被引:8,自引:0,他引:8
Castriota Scanderbeg A Tomaiuolo F Sabatini U Nocentini U Grasso MG Caltagirone C 《AJNR. American journal of neuroradiology》2000,21(5):862-868
BACKGROUND AND PURPOSE: Conventional MR imaging does not provide specific information that can be reliably associated with the pathologic substrate and clinical status of patients with multiple sclerosis (MS). Our goals were 1) to determine whether the orientationally averaged water diffusion coefficient () can be used to distinguish between plaques of different severity in these patients and 2) to assess possible correlations between values and disease duration, Expanded Disability Status Scale (EDSS) score, and signal intensity on T1-weighted MR images. METHODS: Twenty patients (10 with relapsing-remitting MS and 10 with secondary-progressive MS) and 11 healthy volunteers underwent a combined conventional and diffusion-weighted MR study of the brain. , a parameter that is proportional to the trace of the diffusion tensor, was computed by averaging the apparent diffusion coefficients measured in the x, y, and z directions. measurements were obtained for selected areas of white matter plaques. Differences in among the three groups were tested using analysis of variance. RESULTS: was significantly higher (1.445 +/- 0.129 x 10(-3) mm2/s) in secondary-progressive lesions than in relapsing-remitting lesions (0.951 +/- 0.08), and both values were higher than in normal white matter (0.732 +/- 0.02). There was a significant negative correlation between and the degree of hypointensity on T1-weighted images, and a positive correlation between and both EDSS score and disease duration. CONCLUSION: Our findings suggest that is useful for distinguishing MS lesions of different severities, which are associated with different degrees of clinical disability. 相似文献
90.
GA McCarthy B Kampmann V Novelli RF Miller DE Mercey D Gibb 《Archives of disease in childhood》1996,74(5):455-457
AIDS related Kaposi's sarcoma is commonly seen in homosexual men, only occasionally in men and women with heterosexually acquired HIV, and extremely rarely in children. The case of an HIV infected mother and her vertically infected child who both developed visceral Kaposi's sarcoma is reported. It is proposed that the putative Kaposi's sarcoma agent may also be transmitted vertically. 相似文献