全文获取类型
收费全文 | 953篇 |
免费 | 51篇 |
国内免费 | 2篇 |
专业分类
耳鼻咽喉 | 11篇 |
儿科学 | 33篇 |
妇产科学 | 33篇 |
基础医学 | 110篇 |
口腔科学 | 45篇 |
临床医学 | 49篇 |
内科学 | 130篇 |
皮肤病学 | 5篇 |
神经病学 | 105篇 |
特种医学 | 22篇 |
外科学 | 186篇 |
综合类 | 32篇 |
预防医学 | 65篇 |
眼科学 | 15篇 |
药学 | 116篇 |
中国医学 | 8篇 |
肿瘤学 | 41篇 |
出版年
2023年 | 3篇 |
2022年 | 13篇 |
2021年 | 23篇 |
2020年 | 20篇 |
2019年 | 19篇 |
2018年 | 18篇 |
2017年 | 14篇 |
2016年 | 28篇 |
2015年 | 14篇 |
2014年 | 37篇 |
2013年 | 45篇 |
2012年 | 45篇 |
2011年 | 61篇 |
2010年 | 29篇 |
2009年 | 21篇 |
2008年 | 40篇 |
2007年 | 62篇 |
2006年 | 44篇 |
2005年 | 35篇 |
2004年 | 35篇 |
2003年 | 56篇 |
2002年 | 30篇 |
2001年 | 28篇 |
2000年 | 18篇 |
1999年 | 16篇 |
1998年 | 11篇 |
1997年 | 9篇 |
1996年 | 13篇 |
1995年 | 3篇 |
1994年 | 10篇 |
1993年 | 6篇 |
1992年 | 12篇 |
1991年 | 16篇 |
1990年 | 14篇 |
1989年 | 14篇 |
1988年 | 17篇 |
1987年 | 14篇 |
1986年 | 9篇 |
1985年 | 6篇 |
1984年 | 11篇 |
1983年 | 9篇 |
1982年 | 6篇 |
1981年 | 3篇 |
1979年 | 10篇 |
1978年 | 5篇 |
1977年 | 3篇 |
1971年 | 3篇 |
1967年 | 4篇 |
1966年 | 3篇 |
1944年 | 5篇 |
排序方式: 共有1006条查询结果,搜索用时 15 毫秒
1.
Brain cyclooxygenases (COX), the rate-limiting enzyme in prostaglandin synthesis, is rapidly and transiently induced by convulsions in hippocampal and cortical neurons. Previous studies have explored the protective effect of naproxen (non-selective COX-inhibitor) or rofecoxib (selective COX-2 inhibitor) against chemical kindling in mice. With this background, the present study was designed to explore the possible effect of nimesulide (a preferential COX-2 inhibitor) against pentylenetetrazol (PTZ)-induced kindling epilepsy in mice. To induce kindling, PTZ was injected in a subconvulsive dose (40 mg/kg, i.p.) every other day for 15 days. Nimesulide (2.5 or 5 mg/kg, p.o.) was administered each day 45 min before either PTZ or vehicle challenge. The intensity of kindling was assessed immediately after PTZ administration according to a prevalidated scoring scale. On 16th day i.e. 24 h after the last dose of PTZ, animals were sacrificed and various biochemical parameters were assessed in the whole brain. Compared with normal control group, PTZ-kindled mice had significantly higher levels of malondialdehyde, nitrite, myeloperoxidase but had lower levels of reduced glutathione in the whole brain homogenate. Chronic treatment with nimesulide (2.5 or 5 mg/kg, p.o.) for 15 days showed significant decrease in kindling score and could play a role in controlling the accompanying biochemical alterations due to PTZ. These results suggested that nimesulide, a preferential COX-2 inhibitor offered neuroprotection against PTZ-induced kindling in mice. 相似文献
2.
K. R. Afugupalli S. Kalfas S. Edwardsson A. S. Naidu 《Oral microbiology and immunology》1995,10(1):35-41
The interaction of lactoferrin with Actinobacillus actinomycetemcomitans was examined in a 125 I-labeled protein binding assay. The binding of human and bovine lactoferrins reached maximum within 1 h. Lactoferrin binding to the bacterium was pH-dependent and reversible. Scatchard analysis indicated the existence of two different types of binding sites on the bacterium, one with a high affinity constant kα =8.8×10−7 M) and the other with a low one (kα =1.8×10−6 M). Bacteria in the exponential phase of growth showed higher binding than cells in the stationary phase. Bacteria grown in medium containing serum and/or lysed erythrocytes bound lactoferrin to a lesser extent. Heat-inactivated serum, lysed erythrocytes and other proteins such as mucin and laminin inhibited lactoferrin binding to A. actinomycetemcomitans in a competitive binding assay. Sodium dodecyl sulfate polyacrylamidegel electrophoresis and Western blot analysis of the cell envelope as well as the outer membrane of A. actinomycetemcomitans revealed lactoferrin-reactive protein bands at 29 kDa and 16.5 kDa. The 29-kDa band displayed a heat-modifiable lactoferrin-reactive form with a molecular weight of 34 kDa. Neither proteinase K-treated cell envelope nor lipopolysaccharide of this bacterium showed reactivity with lactoferrin. These data suggests a specific interaction of lactoferrin with outer membrane proteins of A. actinomycetemcomitans . 相似文献
3.
The purpose of this study was to document thromboelastographic (TEG) changes in abruptio placentae and to compare these results with that of conventional tests used to monitor coagulation. This was a prospective study of 30 patients with abruptio placentae. All coagulation investigations including the TEG were performed on admission, immediately following delivery, and after periods of 4 hours and 24 hours. Results showed that standard coagulation tests detected coagulation abnormalities except the platelet count returned to normal limits within 24 hours of delivery. There was strong correlation between fibrinogen levels and the TEG parameters, ma and k time (r=0.8). There was moderate correlation between platelet count and ma (r=0.6). In conclusion, minor abnormalities in the clotting profile are clinically unimportant. The TEG does not detect such minor abnormalities because of its inherent ability to test the coagulation cascade as a whole. Major abnormalities are clinically relevant and the TEG detect 75% of them. Further, the TEG establishes the diagnosis of hypercoagulability an early sign of disseminated intravascular coagulation. Although standard laboratory tests are still necessary to detect coagulation abnormalities on admission, the TEG is a useful test in large obstetric units where laboratory results are not immediately available for the purposes of monitoring and treating ongoing coagulation defects. 相似文献
4.
5.
Particle agglutination assays for rapid detection of fibronectin, fibrinogen, and collagen receptors on Staphylococcus aureus. 总被引:4,自引:5,他引:4 下载免费PDF全文
Latex beads (0.8-micron diameter; Difco Laboratories) were coated with fibronectin, fibrinogen, collagen type I, or denatured collagen (gelatin) and evaluated in a particle agglutination assay (PAA) for the rapid detection of fibronectin, fibrinogen, or collagen binding to Staphylococcus aureus. These assays were compared with a commercial test for detecting the binding of fibrinogen and immunoglobulin G (Staphaurex). Bacterial cells (approximately 10(10) cells per ml) suspended in 0.02 M potassium phosphate buffer (pH 6.8) caused the clumping of standard fibronectin, collagen, gelatin, and fibrinogen latex suspensions within 2 min on glass slides. The test results were scored semiquantitatively from strongly positive ( ) to weakly positive (+) and negative (-) reactions. The negative PAA reactions corresponded to a median value of 11.5% relative to the binding of 125I-labeled protein to strain Cowan 1, indicating the high sensitivity of the test. The reactions with fibronectin and fibrinogen latex suspensions and with Staphaurex were optimal for cells grown on tryptic soy and brain heart infusion broth media. Blood agar was optimal for reactions with collagen and gelatin latex suspensions. Media containing high salts (mannitol salt agar and staphylococcus medium 110) enhanced the tendency of cells to autoaggregate. These assays were also clinically evaluated on 187 S. aureus isolates. The PAA reagents were stable, and the assays were highly specific, sensitive, and reproducible, thus making PAA suitable for the rapid screening of the binding of various bacterial pathogens to serum and connective-tissue proteins. 相似文献
6.
Collagen binding, elastase production, and slime production associated with coagulase-negative staphylococci isolated from bovine intramammary infections. 下载免费PDF全文
Collagen binding, elastase production, slime production, and associated somatic cell counts were determined with 160 strains of coagulase-negative staphylococci isolated from bovine intramammary infections. Mean binding values for type I and II collagen with Staphylococcus epidermidis, S. chromogenes, and S. hyicus strains were 5.8, 6.6, and 7.4 and 4.3, 4.2, and 4.9%, respectively. Eleven of 28 (39.3%) S. epidermidis, 1 of 38 (2.6%) S. chromogenes, and 1 of 94 (1.1%) S. hyicus strains were elastase positive. Slime production was noted with 12 (42.9%) S. epidermidis, 1 (2.6%) S. chromogenes, and 11 (11.7%) S. hyicus strains. No differences in somatic cell counts were observed with type I or type II collagen binding, elastase production, or slime production with S. epidermidis or S. chromogenes. However, somatic cell counts associated with S. hyicus strains with collagen type I binding affinities of greater than 5 and type II binding affinities of greater than 3 were 320.7 x 10(3) compared with 163.9 x 10(3) for strains with lower binding affinities. 相似文献
7.
Cellular localization of simian immunodeficiency virus in lymphoid tissues. II. In situ hybridization 总被引:7,自引:11,他引:7 下载免费PDF全文
M S Wyand D J Ringler Y M Naidu M Mattmuller L V Chalifoux P K Sehgal M D Daniel R C Desrosiers N W King 《The American journal of pathology》1989,134(2):385-393
Lymph nodes and spleens were collected at autopsy and by biopsy from 29 rhesus monkeys infected with simian immunodeficiency virus (SIV). Lymph nodes were classified morphologically into stages of follicular hyperplasia, follicular involution, follicular depletion with normal or expanded paracortices, follicular and paracortical depletion, granulomatous lymphadenitis, or normal. The distribution of SIV RNA was determined by in situ hybridization using a nick translated, 35S labeled, SIVmac DNA probe. Numbers of SIV-infected cells were rare during follicular hyperplasia, numerous during follicular and paracortical expansion, and rare during follicular and paracortical depletion. The splenic morphology reflected that of the lymph nodes; however, the numbers of SIV-positive cells were uniformly lower. SIV RNA was frequently restricted to a single nucleus within multinucleate syncytial cells in two cases of granulomatous lymphadenitis. These results, combined with those of a previous study, provide evidence for antigen trapping in SIV-infected hyperplastic lymph nodes and for widespread viral infection of macrophages and lymphocytes during paracortical expansion. 相似文献
8.
The adrenoleukodystrophies 总被引:2,自引:0,他引:2
Clinical, biochemical, and genetic studies of adrenoleukodystrophy (ALD) are of current interest for six main reasons. First, assays of plasma lipids or cultured skin fibroblasts or amniocytes permit precise diagnosis of persons affected by the disease, as well as prenatal diagnosis and carrier detection. Second, the general nature of the enzymatic defect has been identified and the ALD gene has been mapped to the q28 segment of the X-chromosome. Third, the disease is more common than had been previously recognized. We have identified 350 patients in over 200 kindreds. Fourth, phenotypic variability is a striking feature. The illness may present as a rapidly fatal neurological disorder in early childhood or as a chronic progressive paraparesis in young, middle-aged, or even older adults. The latter syndrome is referred to as adrenomyeloneuropathy (AMN). It is of particular interest that these variants occur regularly within the same kindred, so that the phenotypic variation cannot be attributed to different genetic mutations. A fifth feature of interest is that in this X-linked disorder 12 to 40% of female carriers show various degrees of neurological disability, although almost always milder than in the hemizygous male. Studies with cultured fibroblasts suggest that mutant ALD cell lines have a competitive advantage over normal cell lines, a phenomenon which has not been observed in any other disorder. Finally, ALD appears to be one example of a peroxisomal disorder. Knowledge about the normal function of this subcellular organelle has emerged only recently, and further studies of ALD and related disorders will contribute to this. 相似文献
9.
Glioblastoma (GBM) is the most malignant brain tumor and accounts for most adult brain tumors. Current available treatment options for GBM are multimodal, which include surgical resection, radiation, and chemotherapy. Despite the significant advances in diagnostic and therapeutic approaches, GBM remains largely resistant to treatment, with a poor median survival rate between 12 and 18 months. With increasing drug resistance, the introduction of phytochemicals into current GBM treatment has become a potential strategy to combat GBM. Phytochemicals possess multifarious bioactivities with multitarget sites and comparatively marginal toxicity. Among them, curcumin is the most studied compound described as a potential anticancer agent due to its multi-targeted signaling/molecular pathways properties. Curcumin possesses the ability to modulate the core pathways involved in GBM cell proliferation, apoptosis, cell cycle arrest, autophagy, paraptosis, oxidative stress, and tumor cell motility. This review discusses curcumin’s anticancer mechanism through modulation of Rb, p53, MAPK, P13K/Akt, JAK/STAT, Shh, and NF-κB pathways, which are commonly involved and dysregulated in preclinical and clinical GBM models. In addition, limitation issues such as bioavailability, pharmacokinetics perspectives strategies, and clinical trials were discussed. 相似文献
10.
In four cases of the Rett syndrome (RS) (age 3 1/2, 6, 11 and 12 years), paroxysmal activity and especially spike discharges over the central region could be blocked or attenuated by passive finger movements. This response, however, is not demonstrable in the majority of children with RS. The blocking or attenuating effect of passive movements is compared with earlier observations of central spike discharges occurring in children with benign Rolandic epilepsy. In some of these children, central spikes could be blocked by active hand movements. It was assumed that such a positive blocking response underscores the "functional" ("dysfunctional") character of the Rolandic spikes and the lack of local structural damage. In children with cerebral palsy, seizures and central spike (and evidence of structural brain damage), such a blocking response was not obtainable. Taking into consideration these earlier observations, there is reason to presume that the central spike activity found in RS is based on dysfunction rather than on structural impairment. 相似文献