全文获取类型
收费全文 | 4204篇 |
免费 | 201篇 |
国内免费 | 26篇 |
专业分类
耳鼻咽喉 | 57篇 |
儿科学 | 43篇 |
妇产科学 | 42篇 |
基础医学 | 704篇 |
口腔科学 | 24篇 |
临床医学 | 317篇 |
内科学 | 1185篇 |
皮肤病学 | 84篇 |
神经病学 | 369篇 |
特种医学 | 147篇 |
外科学 | 398篇 |
综合类 | 17篇 |
一般理论 | 1篇 |
预防医学 | 271篇 |
眼科学 | 90篇 |
药学 | 343篇 |
中国医学 | 32篇 |
肿瘤学 | 307篇 |
出版年
2023年 | 28篇 |
2022年 | 97篇 |
2021年 | 191篇 |
2020年 | 72篇 |
2019年 | 95篇 |
2018年 | 115篇 |
2017年 | 83篇 |
2016年 | 93篇 |
2015年 | 94篇 |
2014年 | 126篇 |
2013年 | 191篇 |
2012年 | 293篇 |
2011年 | 272篇 |
2010年 | 151篇 |
2009年 | 142篇 |
2008年 | 245篇 |
2007年 | 240篇 |
2006年 | 239篇 |
2005年 | 232篇 |
2004年 | 224篇 |
2003年 | 169篇 |
2002年 | 200篇 |
2001年 | 31篇 |
2000年 | 30篇 |
1999年 | 34篇 |
1998年 | 23篇 |
1996年 | 25篇 |
1995年 | 21篇 |
1994年 | 17篇 |
1993年 | 20篇 |
1992年 | 32篇 |
1991年 | 34篇 |
1990年 | 38篇 |
1989年 | 29篇 |
1988年 | 39篇 |
1987年 | 29篇 |
1986年 | 30篇 |
1985年 | 37篇 |
1984年 | 32篇 |
1983年 | 29篇 |
1981年 | 18篇 |
1979年 | 29篇 |
1978年 | 24篇 |
1977年 | 20篇 |
1975年 | 16篇 |
1974年 | 23篇 |
1973年 | 24篇 |
1972年 | 16篇 |
1971年 | 15篇 |
1968年 | 15篇 |
排序方式: 共有4431条查询结果,搜索用时 15 毫秒
21.
Polysomnographic and actigraphic evidence of sleep fragmentation in patients with irritable bowel syndrome 总被引:3,自引:0,他引:3
STUDY OBJECTIVE: To characterize the function and quality of sleep in patients with irritable bowel syndrome (IBS). DESIGN: A prospective study with a historic comparison group. SETTING: A regional hospital that also serves as a tertiary referral center. PATIENTS: Eighteen patients with IBS and a comparison group of 20 matched adults with mild benign snoring. INTERVENTIONS: A polysomnography study and a wrist actigraphy study. MEASUREMENTS: All subjects underwent sleep studies and completed self-report questionnaires (IBS severity, psychosocial variables, sleep function, and Epworth Sleepiness Scale). Fourteen IBS and 11 comparison patients underwent actigraphy. RESULTS: The IBS patients had more than 70% less slow-wave stage sleep (4.5 +/- 7.3% vs 19.3 +/- 12.9%; P = 0.006), compensated by increased stage 2 sleep (72.2 +/- 6.6% vs 60.1 +/- 16.8%; P = 0.01). The IBS group had significant sleep fragmentation with a significantly higher arousal and awakening index (P < 0.001), a longer wake period after sleep onset (P = 0.02), and more downward shifts to lighter sleep stages (P = 0.01). The 4-night actigraphy study supported the polysomnography findings. The sleep fragmentation index was significantly higher (P = 0.008) in the IBS group. The IBS patients reported greater daytime sleepiness (9.0 +/- 4.8 vs 6.4 +/- 4.8, Epworth Sleepiness Scale score, P < 0.01) and greater impairment in quality of life, which correlated significantly with the sleep fragmentation indexes. The difference between the groups was not due to differences in baseline anxiety/depression levels. CONCLUSIONS: Patients with IBS have impaired sleep quality, reduced slow-wave sleep activity, and significant sleep fragmentation. The cause-and-effect relationship of these findings with patients' daytime symptoms should be studied further. 相似文献
22.
Ueno T Tremblay J Kunes J Zicha J Dobesova Z Pausova Z Deng AY Sun YL Jacob HJ Hamet P 《Journal of molecular medicine (Berlin, Germany)》2003,81(1):51-60
Acute pharmacogenetic analysis was carried out in an intercross F2 population derived from Prague hypertensive-hypertriglyceridemic and Lewis rats. Quantitative trait loci (QTL) mapping was performed for baseline blood pressure (BP) and for BP after blockade of the renin-angiotensin system by losartan, of the sympathetic nervous system (SNS) by pentolinium, and of the nitric oxide system by N(G)-nitro- L-arginine methyl ester. Two significant loci for baseline BP were found on chromosome (Chr) 3 (logarithm of likelihood, LOD, 3.8) and Chr 5 (LOD 3.6), and one suggestive locus on Chr 1 (LOD 2.7). The QTL on Chr 3 persisted after treatment with the three agents while the QTL on Chr 5 and Chr 1 disappeared after pentolinium administration. This suggests independence of the locus on Chr 3 from each acute BP regulatory system examined, whereas the loci on Chr 5 and Chr 1 appeared to be controlled mainly by the SNS. Although not apparent at baseline, a significant locus appeared on Chr 8 (LOD 7.0) after blockade of the SNS, and NO system blockade led to the appearance of a new QTL on Chr 1 (LOD 3.6), indicating the contribution of the inhibited systems to these loci. Pharmacogenetic dissection of the BP trait is a powerful tool to unravel the underlying physiological mechanisms of QTL affecting baseline BP and to identify specific QTL for the response to drugs. This pharmocogenetic approach enabled us to determine the main causative acute BP regulatory systems and should lead to better selection of suitable antihypertensive drugs for individual patients. 相似文献
23.
24.
Robert I. Fox Mario Luppi Ho-Il Kang Pavel Pisa 《Springer Seminars in Immunopathology》1991,13(2):217-231
Summary Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by severe dryness of the eyes and mouth, resulting from lymphocytic infiltration of the lacrimal and salivary glands. SS may exist as a primary condition (primary SS, 1° SS) or as a secondary condition (2° SS) in association with rheumatoid arthritis, systemic lupus erythematosus, or progressive systemic sclerosis. In some 1° SS patients, there may be involvement of the extraglandular organs, including skin, kidney, liver, lung and nervous system. Furthermore, these patients may develop a lymphoproliferative syndrome that includes lymphadenopathy and increased risk of lymphoma. In the pathogenesis of SS, a role for Epstein-Barr virus (EBV) has been suggested because: (a) EBV is present in salivary gland epithelial cells of normal individuals and exaggerated immune responses against EBV could play a role in the destruction of salivary glands in SS; (b) SS salivary gland biopsies contain increased levels of EBV DNA in comparison to normal salivary glands, indicating viral reactivation and inability of lymphoid infiltrates to control EBV replication in SS patients; and (c) salivary gland epithelial cells in SS patients express high levels of HLA-DR antigens and may present EBV-associated antigens to immune T cells in SS patients. Therefore, SS may represent a situation in which genetically predisposed individuals (i. e., HLA-DR3-DQA4-DQB2) have a persistent but ineffectual T cell immune response against EBV at its site of latency. Among 14 non-Hodgkin's lymphomas that developed in SS patients, EBV DNA was detected in increased amounts in the tumor tissue of one patient. Characterization of this tumor DNA revealed: (a) polyclonal immunoglobulin gene rearrangements; (b) EBV DNA with an unusual restriction fragment length polymorphism pattern involving the Bam M fragment; and (c) EBV terminal repeat sequences suggestive of viral replication, similar to those reported in EBV lymphomas occurring in other immunocompromised individuals. Early recognition of this clinical problem may allow beneficial use of antiviral agents. 相似文献
25.
Jiří Bártek Vladimir Viklický František Franěk Pavla Angelisová Pavel Dráber Taťána Jarošíková Miloš Němec Hana Verlová 《Immunology letters》1982,4(5):231-235
Five stable hybridoma lines were prepared using the myeloma cell line P3-X63-Ag.653 and spleen cells of mice hyperimmunized by pig transferrin. All hybridomas grew well in mouse peritoneal cavity and produced antibodies of the IgG1 subclass. Antibody preparations obtained from ascitic fluids tested for their capacity of antigen precipitation. No precipitation was obtained with single antibodies and with pairs of antibodies. Three out of 10 possible triads gave clear and sharp precipitation zones and rings in immunodiffusion tests performed in agar gel. All 5 antibodies were shown by quantitative enzyme-immunoassay to be specific for pig transferrin: no cross-reaction was obtained with mouse, human, horse and sheep transferrins. 相似文献
26.
A study of the x-ray sensitivity of amorphous selenium (a-Se) for digital mammography has been performed. A uniform layer of a-Se was deposited on a glass substrate with electrodes on both surfaces. The deposition procedure was identical to that used for a-Se flat-panel detectors. A high voltage was applied to the top surface of the a-Se layer in order to establish an electric field E(Se). Then the sample was exposed to x rays with 27 kVp spectra generated from an x-ray tube with a molybdenum (Mo) target. The mean x-ray energy of the spectrum used was approximately 16.6 keV. The x-ray current generated by the a-Se layer was measured as a function of E(Se). From the current measurement and the estimation of total x-ray energy absorbed in the a-Se, the energy required to create one electron-hole pair (EHP), W, was determined as a function of E(Se). It was found that at the most commonly used E(Se) of 10 V/microm, W was measured as 64 eV. This is considerably higher than the widely accepted typical value of W = 50 eV measured at higher x-ray photon energies (e.g., 50 keV). The dependence of W as a function of E(Se) can be best fitted using the empirical expression of E(Se)-gamma. This relationship is consistent with the results obtained at higher x-ray energies. This article provides an accurate measurement of x-ray sensitivity of a-Se at mammographic energies independent of detector operation, such as the most recently developed flat-panel detectors. The results will be a useful tool for investigation and optimization of a-Se-based x-ray imaging detectors, such as determination of pixel fill-factor and optimal E(Se) during operation. 相似文献
27.
Apoptotic body engulfment by a human stellate cell line is profibrogenic 总被引:22,自引:0,他引:22
Canbay A Taimr P Torok N Higuchi H Friedman S Gores GJ 《Laboratory investigation; a journal of technical methods and pathology》2003,83(5):655-663
Hepatocyte apoptosis and stellate cell activation are both features of chronic liver diseases, but a relationship between these events has not been explored. In macrophages, engulfment of apoptotic bodies induces expression of transforming growth factor-beta (TGF-beta), a profibrogenic cytokine. We examined whether a similar response occurs in stellate cells. Fluorescently labeled hepatocyte apoptotic bodies were added to cultures of primary and immortalized human stellate cells. Stellate cells, but not hepatocytes, readily engulfed apoptotic bodies in a time-dependent manner as assessed by confocal microscopy. The activation of primary and immortalized human stellate cells after incubation with apoptotic bodies, as well as their fibrogenic activity, was indicated by an increase in alpha-smooth muscle actin (primary cells), TGF-beta1, and collagen alpha1(I) mRNA (primary and immortalized cells). The profibrogenic response was dependent upon apoptotic body engulfment, because nocodazole, a microtubule-inhibiting agent, blocked both the engulfment and the increase of TGF-beta1 and collagen alpha1(I) mRNA. As described in primary rodent stellate cells, up-regulation of collagen alpha1(I) mRNA was inhibited by a PI-3K inhibitor (LY294002) and a p38 mitogen-activated protein kinase inhibitor (SB203580) in LX-1 cells. In conclusion, these data support a model in which engulfment of hepatocyte apoptotic bodies by stellate cells leads to a fibrogenic response by eliciting a kinase-signaling pathway. 相似文献
28.
Cervinková Z Radvaková D Kohout P 《Acta medica (Hradec Králové) / Universitas Carolina, Facultas Medica Hradec Králové》2002,45(1):13-18
The aim of our study was to evaluate the impact of impaired barrier function of the small intestine induced by indomethacin on biochemical markers of liver damage (serum levels of alanine aminotransferase, aspartate aminotransferase, bilirubin), and liver functional parameters (serum concentration of albumin, liver DNA synthesis). Indomethacin (Sigma) was administered in 2 injections in a dose of 7.5 mg/kg subcutaneously spaced 24 hours apart, rats were sacrificed 24, 48 or 72 hours after the second dose of indomethacin. Control rats received indomethacin vehicle (5% NaHCO3, pH 7.4, 1.0 ml/kg) in the same manner. Small intestine injury was approved by increased permeability (measured as a lactulose-mannitol index). Significant increase of small intestine DNA synthesis (estimated by incorporation of 3H thymidine) in indomethacin-treated rats 48 (p < 0.01) and 72 (p < 0.05) hours after the second dose of indomethacin documents induction of reparative process. All biochemical markers of liver injury were significantly decreased in indomethacin treated rats in all recorded intervals (p < 0.05). By contraries, serum concentration of albumin, which predicates about liver function, was in indomethacin-treated rats significantly decreased in all intervals (p < 0.01). To explain these contrarious results of indomethacin-induced impaired barrier function of the small intestine on the liver deserves further studies. 相似文献
29.
Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy is a rare recessive autoimmune disorder caused by a defect in a single gene called AIRE (autoimmune regulator). Characteristics of this disease include a variable combination of autoimmune endocrine tissue destruction, mucocutaneous candidiasis and ectodermal dystrophies. The development of Aire-knockout mice has provided an invaluable model for the study of this disease. The aim of this review is to briefly highlight the strides made in APECED research using these transgenic murine models, with a focus on known roles of Aire in autoimmunity. The findings thus far are compelling and prompt additional areas of study which are discussed. 相似文献
30.
Evidence for linkage of nonsyndromic cleft lip with or without cleft palate to a region on chromosome 2 总被引:4,自引:0,他引:4
Zeiger JS Hetmanski JB Beaty TH VanderKolk CA Wyszynski DF Bailey-Wilson JE de Luna RO Perandones C Tolarova MM Mosby T Bennun R Segovia M Calda P Pugh EW Doheny K McIntosh I 《European journal of human genetics : EJHG》2003,11(11):835-839
Results from a genome-wide screen of 10 multiplex families ascertained through probands with nonsyndromic cleft lip with or without cleft palate (CL/P) in Mexico, Argentina, and the United States yielded suggestive evidence of linkage to chromosomes 2, 6, 17 and 18. Fine mapping excluded all regions except chromosome 2. Subsequent analysis was performed on the original 10 families plus an additional 16 families using 31 markers on chromosome 2. This analysis showed intriguing evidence of linkage to 2q (Zlr=2.26, empirical P-value=0.028 in a chromosome-wide analysis). Transmission disequilibrium tests also revealed evidence of linkage and disequilibrium for two markers in this region (D2S168 and D2S1400 with P-values=0.022 and 0.006, respectively). A subset of these 26 families provided additional evidence for a susceptibility gene for CL/P on 2q, suggesting that further studies of genes in this region are warranted. 相似文献