全文获取类型
收费全文 | 2844篇 |
免费 | 223篇 |
国内免费 | 15篇 |
专业分类
耳鼻咽喉 | 29篇 |
儿科学 | 80篇 |
妇产科学 | 22篇 |
基础医学 | 442篇 |
口腔科学 | 32篇 |
临床医学 | 265篇 |
内科学 | 608篇 |
皮肤病学 | 30篇 |
神经病学 | 164篇 |
特种医学 | 273篇 |
外科学 | 467篇 |
综合类 | 82篇 |
一般理论 | 1篇 |
预防医学 | 161篇 |
眼科学 | 22篇 |
药学 | 167篇 |
中国医学 | 6篇 |
肿瘤学 | 231篇 |
出版年
2021年 | 42篇 |
2019年 | 33篇 |
2018年 | 38篇 |
2017年 | 27篇 |
2016年 | 50篇 |
2015年 | 72篇 |
2014年 | 62篇 |
2013年 | 79篇 |
2012年 | 109篇 |
2011年 | 131篇 |
2010年 | 95篇 |
2009年 | 85篇 |
2008年 | 108篇 |
2007年 | 101篇 |
2006年 | 116篇 |
2005年 | 110篇 |
2004年 | 93篇 |
2003年 | 98篇 |
2002年 | 72篇 |
2001年 | 95篇 |
2000年 | 70篇 |
1999年 | 69篇 |
1998年 | 51篇 |
1997年 | 65篇 |
1996年 | 58篇 |
1995年 | 41篇 |
1994年 | 36篇 |
1993年 | 38篇 |
1992年 | 48篇 |
1991年 | 59篇 |
1990年 | 56篇 |
1989年 | 72篇 |
1988年 | 55篇 |
1987年 | 58篇 |
1986年 | 44篇 |
1985年 | 50篇 |
1984年 | 41篇 |
1983年 | 39篇 |
1982年 | 32篇 |
1981年 | 24篇 |
1980年 | 25篇 |
1979年 | 46篇 |
1978年 | 28篇 |
1977年 | 25篇 |
1976年 | 31篇 |
1974年 | 30篇 |
1973年 | 30篇 |
1972年 | 28篇 |
1971年 | 25篇 |
1970年 | 29篇 |
排序方式: 共有3082条查询结果,搜索用时 453 毫秒
21.
George L. Martin Paul C. Atkins Eliot H. Dunsky Burton Zweiman 《The Journal of allergy and clinical immunology》1980,66(3):204-212
Eleven subjects demonstrating clinical, skin, and inhalation sensitivity to grass or ragweed pollen underwent serial inhalation challenges, with and without orally administered theophylline, terbutaline, and prednisone. Comparisons of antigen sensitivity and mediator release were made during these challenges. All three drugs significantly reduced antigen sensitivity (PD20 inhalation units increasing from 670 to ≧ 3,280). Peak plasma histamine levels after antigen challenge decreased from 11.4 ng/ml to ≦ 3.4 ng/ml during all drug administrations. Similarly, the percent increase in serum neutrophil chemotactic activity (NCA) also decreased, from 96% to ≦ 36% during drug administrations. However, even at antigen doses resulting in bronchospasm during drug administration the systemic appearance of NCA and histamine were reduced. We conclude that prednisone, theophylline, and terbutaline significantly reduce antigen-induced bronchospasm and mediator release. The occurrence of bronchospasm despite the inhibition of histamine and NCA suggests either that the local concentration of these mediators are critical or that other mediators produce the bronchospasm observed. 相似文献
22.
Pathogenesis of fever in delayed hypersensitivity: factors influencing release of pyrogen-inducing lymphokines. 总被引:2,自引:1,他引:2
下载免费PDF全文
![点击此处可从《Infection and immunity》网站下载免费的PDF全文](/ch/ext_images/free.gif)
In continuing studies on the pathogenesis of fever in states of delayed hypersensitivity, we have investigated the conditions for the release of an endogenous pyrogen (EP)-inducing lymphokine from draining-lymph-node lymphocytes of rabbits with delayed hypersensitivity to bovine gamma globulin. Using doses of 4 X 10(7) to 5 X 10(7) blood leukocytes (BL) as a source of EP, we found that ratios of about 5:1 of viable lymphocytes to BL were required to stimulate the BL to produce detectable amounts of EP in vitro. Both irradiated lymphocytes (1,700 R) as well as those from steroid-treated donors retained their ability to activate BL when incubated with antigen, properties consistent with activated "T" lymphocytes. In experiments to determine effects of temperature and duration of incubation on lymphokine release, the maximum EP-releasing activity was found to be present in supernatants of sensitized lymphocytes incubated with antigen for 18 h at 37 degrees C. These studies have confirmed that sensitized lymphocytes release a soluble, pyrogen-inducing lymphokine when incubated with antigen and further demonstrate that tissue macrophages (Kupffer cells) as well as BL can be activated to produce EP in vitro by this agent. 相似文献
23.
24.
25.
IL-1 up-regulates osteopontin expression in experimental crescentic glomerulonephritis in the rat 总被引:11,自引:0,他引:11
下载免费PDF全文
![点击此处可从《The American journal of pathology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Yu XQ Fan JM Nikolic-Paterson DJ Yang N Mu W Pichler R Johnson RJ Atkins RC Lan HY 《The American journal of pathology》1999,154(3):833-841
Osteopontin (OPN) is a macrophage chemotactic and adhesion molecule that acts to promote macrophage infiltration in rat anti-glomerular basement membrane (GBM) glomerulonephritis. The present study investigated the role of interleukin-1 (IL-1) in the up-regulation of renal OPN expression in this disease model. Accelerated anti-GBM glomerulonephritis was induced in groups of six rats. Animals were treated by a constant infusion of the IL-1 receptor antagonist or saline (control) over days -1 to 14 (induction phase) or days 7 to 21 (established disease). In normal rat kidney, OPN was expressed in a few tubules (<5%) and absent from glomeruli. During the development of rat anti-GBM disease (days 7 to 21), there was substantial up-regulation of OPN mRNA and protein expression in glomeruli (>5 cells per glomerular cross-section) and tubular epithelial cells (50-75% OPN-positive). Up-regulation of OPN expression was associated with macrophage accumulation within the kidney, severe proteinuria, loss of renal function, and severe histological damage including glomerular crescentic formation and tubulointerstitial fibrosis. In contrast, IL-1 receptor antagonist treatment of either the induction phase of disease or established disease significantly reduced OPN mRNA and protein expression in glomeruli (/75-85%, P < 0.001) and tubules (/45-60%, P < 0.001). The reduction in OPN expression was associated with significant inhibition of macrophage accumulation and progressive renal injury. In vitro, the addition of IL-1 to the normal rat tubular epithelial cell line NRK52E up-regulated OPN mRNA and protein levels, an effect that was dose-dependent and inhibited by the addition of IL-1 receptor antagonist, thus demonstrating that IL-1 can act directly to up-regulate renal OPN expression. In conclusion, this study provides in vivo and in vitro evidence that IL-1 up-regulates OPN expression in experimental kidney disease and support for the argument that inhibition of OPN expression is one mechanism by which IL-1 receptor antagonist treatment suppresses macrophage-mediated renal injury. 相似文献
26.
Lectins are potentially useful tools in histopathology for the identification of carbohydrates and distinguishing cells according to their type, differentiation or function. Conjugated to fluorescent or enzyme labels, lectins are simple to use on fresh tissue but fixation and processing sequesters glycoconjugates and dissolves out fat-linked sugars. We describe here the use of labelled antibodies to lectins to localise sites of lectin binding and increase sensitivity, combined with trypsin and neuraminidase to reveal sequestered carbohydrates. Absorbing lectins with appropriate sugars establishes the specificity of binding and allows lectins to be used as sensitive and specific reagents. 相似文献
27.
Regulation of the synthesis of Sindbis virus-specified RNA: role of the virion core protein 总被引:3,自引:0,他引:3
Cells infected with seven different RNA+ mutants of Sindbis virus were found to accumulate a virus-specified polypeptide of mol. wt. 144000 (p144) during incubation at the non-permissive temperature, while at the same time synthesis of the virus structural proteins was drastically reduced. Mapping of the tryptic peptides of p144 showed that it contained the amino acid sequences of all the virus structural proteins. At the non-permissive temperature cells infected with the same seven mutants (out of 28 examined) also showed increased synthesis of 26S RNA, the mRNA for the virus structural proteins, relative to 42S RNA, and the virus genome, compared with infections by wild-type virus. We propose that both these phenotypic effects are the results of a single mutational step and that the primary defect in the processing of the virus structural protein precursor induces the relatively increased rate of synthesis of structural protein mRNA. Temperature-shift experiments with mutant-infected cells showed that p144 itself is not the agent of this effect. The failure of exposure to zinc ions to alter the RNA ratio in wild-type virus-infected cells suggested that the virus envelope proteins are not involved either, since their synthesis is preferentially inhibited under these circumstances. It is possible that it is the failure to synthesize the proper quantity of core protein in the mutant-infected cells which causes the shift of RNA synthesis in favour of structural protein mRNA. 相似文献
28.
Double-blind, placebo-controlled food challenge (DBPCFC) as an office procedure: a manual 总被引:12,自引:2,他引:12
S A Bock H A Sampson F M Atkins R S Zeiger S Lehrer M Sachs R K Bush D D Metcalfe 《The Journal of allergy and clinical immunology》1988,82(6):986-997
There is now enough experience with the use of double-blind, placebo-controlled, food challenge (DBPCFC) to recommend its use as an office procedure for most patients complaining of adverse reactions to foods. This manual discusses the practical methods required for the allergist to undertake DBPCFC in the office. Thorough histories supplemented by food allergen skin testing are used to design a DBPCFC that carefully attempts to reproduce the history of food-induced symptoms described by the patient. Precautions that must be taken are delineated before challenge, as is treatment that may be required if a reaction occurs. For those foods to which challenges are positive, longitudinal evaluation with repeated challenge at appropriate intervals help to determine whether or not the problem will resolve over a period of time. 相似文献
29.
30.
CP Schaecher KA Groesch 《American journal of reproductive immunology (New York, N.Y. : 1989)》2006,55(6):405-405
Background: Control of mRNA stability is an essential regulatory process in eukaryotic gene expression. HuR, a 3'UTR mRNA binding protein, can protect AU-rich mRNA from degradation in response to stresses. PlGF, an angiogenic growth factor, contains two consensus AU-rich sites suggesting that under normal conditions HuR may protect PlGF mRNA from degradation. Trophoblast expression of PlGF is significantly decreased in preeclampsia and by hypoxia in vitro . We hypothesize that decreased levels of cytoplasmic HuR may contribute to decreased PlGF expression in hypoxic and preeclamptic trophoblast.
Methods: Western blots were used to determine relative effects of in vitro hypoxia on HuR protein expression and subcellular localization in trophoblast. Immunohistochemistry was used to compare HuR expression patterns in trophoblast of preeclamptic and normal placentae.
Results: Cytoplasmic expression of HuR was decreased 1.4 fold in the cytoplasm and 1.2 fold in the nucleus of JEG3 cells. A shift in HuR was more apparent in primary trophoblast with a greater than 2-fold decrease in the cytoplasm and a 1.4 fold decrease in the nucleus following 24 hr of hypoxia. Immunohistochemical analyses detected HuR expression in near term trophoblast in situ . However, this technical approach did not detect a significant change in HuR expression between normal and preeclamptic trophoblast.
Conclusions: HuR expression is decreased in hypoxic trophoblast, at least in vitro , which may provide a causal link to decreased PlGF mRNA expression. Down regulation of trophoblast PlGF expression is thought to contribute to the pathophysiology associated with preeclampsia including the relative lack of perfusion of the placenta and systemic renal effects. 相似文献
Methods: Western blots were used to determine relative effects of in vitro hypoxia on HuR protein expression and subcellular localization in trophoblast. Immunohistochemistry was used to compare HuR expression patterns in trophoblast of preeclamptic and normal placentae.
Results: Cytoplasmic expression of HuR was decreased 1.4 fold in the cytoplasm and 1.2 fold in the nucleus of JEG3 cells. A shift in HuR was more apparent in primary trophoblast with a greater than 2-fold decrease in the cytoplasm and a 1.4 fold decrease in the nucleus following 24 hr of hypoxia. Immunohistochemical analyses detected HuR expression in near term trophoblast in situ . However, this technical approach did not detect a significant change in HuR expression between normal and preeclamptic trophoblast.
Conclusions: HuR expression is decreased in hypoxic trophoblast, at least in vitro , which may provide a causal link to decreased PlGF mRNA expression. Down regulation of trophoblast PlGF expression is thought to contribute to the pathophysiology associated with preeclampsia including the relative lack of perfusion of the placenta and systemic renal effects. 相似文献