全文获取类型
收费全文 | 2347459篇 |
免费 | 174840篇 |
国内免费 | 3320篇 |
专业分类
耳鼻咽喉 | 32053篇 |
儿科学 | 75920篇 |
妇产科学 | 62709篇 |
基础医学 | 348282篇 |
口腔科学 | 63627篇 |
临床医学 | 211457篇 |
内科学 | 457429篇 |
皮肤病学 | 51742篇 |
神经病学 | 185344篇 |
特种医学 | 88016篇 |
外国民族医学 | 489篇 |
外科学 | 353954篇 |
综合类 | 47510篇 |
现状与发展 | 12篇 |
一般理论 | 849篇 |
预防医学 | 182884篇 |
眼科学 | 54356篇 |
药学 | 175152篇 |
11篇 | |
中国医学 | 4583篇 |
肿瘤学 | 129240篇 |
出版年
2021年 | 19043篇 |
2019年 | 19581篇 |
2018年 | 27113篇 |
2017年 | 20398篇 |
2016年 | 22788篇 |
2015年 | 25669篇 |
2014年 | 36146篇 |
2013年 | 53994篇 |
2012年 | 74755篇 |
2011年 | 79480篇 |
2010年 | 47086篇 |
2009年 | 44601篇 |
2008年 | 74640篇 |
2007年 | 79512篇 |
2006年 | 80335篇 |
2005年 | 77816篇 |
2004年 | 74398篇 |
2003年 | 71709篇 |
2002年 | 69389篇 |
2001年 | 108740篇 |
2000年 | 111451篇 |
1999年 | 93495篇 |
1998年 | 26992篇 |
1997年 | 23661篇 |
1996年 | 24055篇 |
1995年 | 22715篇 |
1994年 | 20895篇 |
1993年 | 19714篇 |
1992年 | 72001篇 |
1991年 | 70069篇 |
1990年 | 68391篇 |
1989年 | 65663篇 |
1988年 | 60302篇 |
1987年 | 59125篇 |
1986年 | 55217篇 |
1985年 | 53004篇 |
1984年 | 39311篇 |
1983年 | 33396篇 |
1982年 | 19859篇 |
1979年 | 35866篇 |
1978年 | 25651篇 |
1977年 | 21231篇 |
1976年 | 20332篇 |
1975年 | 21817篇 |
1974年 | 26148篇 |
1973年 | 24802篇 |
1972年 | 23200篇 |
1971年 | 22037篇 |
1970年 | 20247篇 |
1969年 | 19315篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
BACKGROUND: The responses of mice to the mite allergen Der p 1 have been used to study the mechanisms of allergic sensitization and the development of new types of immunotherapy. Many of the studies require a knowledge of the T cell epitopes, and because Der p 1 is polymorphic, the effect of natural amino acid substitution in the allergen. The intranasal administration of peptides containing T cell epitopes can induce a mucosal tolerance but it is not known if the major activity is limited to stimulatory peptides and if, as found for autoimmunity, some epitopes are not inhibitory. OBJECTIVE: To determine and compare the sequences of Der p 1 which contain stimulatory epitopes for the high responding H-2(b) and H-2(q) mice and the sequences which induce tolerance by intranasal administration of peptides. METHODS: T cell responses of mice immunized with Der p 1 were measured by in vitro T cell stimulation assays so an extensive study of epitope recognition and intranasal tolerance could be made. Synthetic peptides were used to examine the stimulatory and inhibitory ability of all Der p 1 sequences and to map the major H-2(b) epitope in detail. This included the effect of the common polymorphic amino acid 124 substitution found within this epitope. RESULTS: Three and two regions, respectively, were found to contain stimulatory T cell epitopes for H-2(b) and H-2(q) mice. The peptides in these regions were also the most active at inducing intranasal tolerance for the responding haplotype. The correspondence between inhibitory and stimulatory peptides was maintained for the fine mapping of the major H-2(b) epitope. This was found about a core region of 118-126 which was overlapping but separate to a consensus sequence for the binding of endogeneous peptides. Peptides with alanine at the naturally polymorphic residue 124 stimulated and inhibited responses to Der p 1 more effectively, while peptides with the valine 124 variant were immunogenic but poorly cross-reactive. CONCLUSIONS: The intranasal administration of peptides representing each of five epitopes recognized by two strains of mice were able to induce mucosal tolerance and the major tolerizing activity was limited to these epitopes. The position of the core major epitope for C57 mice, which differs from a previously predicted epitope, and its specificity for the natural alanine 124 variant is described. 相似文献
992.
B. Tutluolu S. At A. N. Anakkaya E. Altu G. A. Tosun M. Yaman 《Clinical and experimental allergy》2002,32(8):1170-1173
OBJECTIVE: This study aimed to investigate the rate of occupational sensitization to horse hair in grooms and whether occupational exposure to horse hair increases respiratory and allergic symptoms and affects lung function in grooms or not. METHODS: This is a cross-sectional study. Two hundred grooms were randomly selected among 1000 grooms working in Veliefendi Hippodrome of Istanbul. One hundred and twenty-five subjects agreed to enter the study. Ninety-two workers who worked in the different parts of this hippodrome enrolled as the control group. A detailed questionnaire including respiratory and allergic symptoms was filled in, physical examination, skin prick tests and pulmonary function tests were performed. RESULTS: Sensitization to horse hair was 12.8% in grooms and 4.3% in controls. The difference was statistically significant (P = 0.0035). Asthma was found in 14.4% of the grooms and 5.4% of the controls, allergic rhinitis in 42.4% of the grooms and 18.4% of the controls, allergic conjunctivitis in 35.2% of the grooms and 15.2% of the controls, and allergic skin diseases in 32.8% of the grooms and 13% of the controls. The differences were statistically significant (P = 0.043, P = 0.0002, P = 0.001 and P = 0.0008, respectively). The means of FEV1, FEV1/FVC and FVC parameters were significantly lower in the groom group (P = 0.006, P = 0.001 and P = 0.003, respectively). In the multivariate analysis, being in the groom group and working years were found to be predictive factors for impairments of lung function (P < 0.001 and P = 0.002, respectively). CONCLUSION: Occupational exposure to horse increases the sensitization to horse hair, induces asthma and allergic symptoms and also impairs lung functions. 相似文献
993.
A. O. Azghani J. W. Baker S. Shetty E. J. Miller G. J. Bhat 《Inflammation research》2002,51(10):506-510
OBJECTIVE AND DESIGN: Bacterial products as well as the host airway inflammatory responses contribute to the pathogenesis of Pseudomonas infections. We sought to determine if Pseudomonas elastase (PE) induces mitogen-activated protein (MAP) kinase activity in association with interleukin-8 (IL-8) production by alveolar epithelial cells. METHODS: We utilized Western blot analysis to detect phosphorylation of signaling intermediates and ELISA was used to measure IL-8 production. RESULTS: We found that PE induces phosphorylation of the extracellular signal-regulated (ERK1/2) proteins of the MAPK pathway in A549 epithelial cells. Similar results were obtained using primary cultures of rabbit alveolar type II epithelial cells. PE also enhanced IL-8 production, which was abolished in the presence of the ERK activation inhibitor U0126. CONCLUSIONS: We conclude that PE activates the ERK1/2 arm of the MAPK pathway and that activation of this pathway results in enhanced IL-8 production. The results demonstrate that PE may augment pulmonary inflammation via cellular signaling that regulates expression of IL-8. 相似文献
994.
B. Bogin P. Smith A.B. Orden M.I. Varela Silva J. Loucky 《American journal of human biology》2002,14(6):753-761
Maya families from Guatemala migrated to the United States in record numbers from the late 1970s to the early 1990s. Births to Maya immigrant women have created a sizable number of Maya American children. The height and sitting height of 5 to 12 years children (n = 431) were measured in 1999 and 2000. Leg length was estimated and the sitting height ratio was calculated. These data were compared with a sample of Maya children living in Guatemala measured in 1998 (n = 1,347). Maya American children are currently 11.54 cm taller and 6.83 cm longer‐legged, on average, than Maya children living in Guatemala. Consequently, the Maya Americans have a significantly lower average sitting height ratio (i.e., relatively longer legs in proportion to length of the head and trunk) than do the Maya in Guatemala. These results add support to the hypothesis that both the height and body proportions of human populations are sensitive indicators of the quality of the environment for growth. Am. J. Hum. Biol. 14:753–761, 2002. © 2002 Wiley‐Liss, Inc. 相似文献
995.
Neutrophil defensins stimulate the release of cytokines by airway epithelial cells: modulation by dexamethasone 总被引:5,自引:0,他引:5
S. van Wetering S. P. G. Mannesse-Lazeroms M. A. J. A. van Sterkenburg P. S. Hiemstra 《Inflammation research》2002,51(1):8-15
OBJECTIVE AND DESIGN: Neutrophils may contribute to recruiting other cells to sites of inflammation by generating chemotactic signals themselves, or by stimulating other cell types to release chemoattractants such as interleukin-8 (IL-8). Recently, we demonstrated that neutrophil-derived alpha-defensins are able to increase IL-8 expression in airway epithelial cells. In addition, it has previously been reported that neutrophil elastase-induced IL-8 synthesis was insensitive to inhibition by the glucocorticoid dexamethasone. The aim of the present study was to investigate the effect of defensins on the expression of various cytokines in cultured airway epithelial cells and to examine the effect of dexamethasone on defensin-induced cytokine synthesis in these cells. METHODS: Cultures of A549 cells and primary bronchial epithelial cells (PBEC) were stimulated with defensins either alone or in the presence of dexamethasone. Supernatants were analyzed for IL-8, ENA-78, IL-6, MCP-1 and GM-CSF by ELISA. In addition, IL-8 and ENA-78 mRNA was detected by Northern blot analysis. RESULTS: Defensins increased IL-8 expression, ENA-78, MCP-1 and GM-CSF release from A549 cells, whereas in PBEC only IL-8 and IL-6 were increased. Pre-treatment with dexamethasone significantly reduced defensin-induced IL-6, IL-8 and ENA-78 synthesis in airway epithelial cells. In addition, dexamethasone also reduced the neutrophil chemotactic activity in supernatants of these cells. CONCLUSIONS: The results from the present study indicate that defensins differentially induce cytokine secretion by A549 cells and PBEC. Glucocorticoids may interfere with the defensin-induced inflammatory process by reducing defensin-induced cytokine secretion in lung epithelial cells. 相似文献
996.
The T-cell receptor (TCR) repertoire plays an important role in shaping specific immune responses. Genetic polymorphisms at the TCR locus, in both constant and variable regions, seem to represent an important mechanism for generating inter-individual and inter-population differences. Considering the scarcity of immune parameters characterized for normal human populations, we decided to determine the frequency of two TCRBV polymorphisms (located in the TCRBV3S1 and TCRBV18 gene segments) in two ethnically distinct groups of the general Brazilian population. Both polymorphisms are related to the expression of these segments at the T-cell surface and can consequently modulate the T-cell repertoire, potentially modifying the capacity of a given individual to develop an immune response. These DNA polymorphisms were analysed in material obtained from adult, normal South-American Caucasoid and Black individuals. A total of 139 individuals were analysed for the TCRBV3S1 and 141 for the TCRBV18 gene segment polymorphisms. The data indicated statistically significant differences in allelic frequencies for the two ethnic groups analysed, suggesting that any correlation between TCR usage or T-cell repertoire and development of a given disease should take in account the ethnic origin of the population studied. 相似文献
997.
Prevention of Bone Loss by Clodronate in Early Postmenopausal Women with Vertebral Osteopenia: A Dose-Finding Study 总被引:1,自引:0,他引:1
M. J. V?lim?ki K. Laitinen K. Laitinen A. Patronen H. Puolijoki H. Puolijoki J. Sepp?nen L. Pylkk?nenand the Probone Study Group 《Osteoporosis international》2002,13(12):937-947
This double-masked, placebo-controlled study was undertaken to determine the efficacy and safety of oral clodronate in the
prevention of bone loss in early postmenopausal women with vertebral osteopenia. Altogether 610 women with a mean age of 53
years were recruited for the study. They were 1–5 years postmenopausal and their lumbar spine bone mineral density (BMD) was
at least 1 standard deviation below the mean of premenopausal women (T-score ≤−1). The subjects were randomized into five study groups to receive either placebo, clodronate 65 mg, 400 mg or 800
mg daily, or intermittent clodronate in 3 month cycles with 400 mg daily for 15 days followed with no treatment for 75 days
for 3 years. One hundred and eighty-seven of 509 women who completed the primary study continued in the extension study of
2 years in which previous placebo users were switched to clodronate 800 mg daily, while previous users of 400 mg or 800 mg
of clodronate used either placebo or 800 mg of clodronate daily. In the primary study clodronate was administered in the evening,
and in the extension 1 h before breakfast on an empty stomach. In the primary study mean changes in lumbar spine BMD were
−3.4% in the placebo group and +0.4% in 800 mg clodronate group [difference between groups at 3 years 3.8% (95% CI 2.7% to
4.9%, p<0.0001)], and in the trochanter area BMD −1.1% in the placebo group, and + 0.4% in the 800 mg clodronate group [difference
between groups at 3 years 1.5% (95% CI 0.05% to 2.9%)]. During the extension study mean changes in lumbar spine BMD were +1.5%
in the clodronate group and −0.2 % in the placebo group [difference between groups 1.7% (CI 0.4% to 3.0%, p = 0.010)] and in trochanter BMD were +2.5% in the clodronate group and no change in the placebo group [difference between
groups 2.1% (CI 0.3% to 3.9%, p = 0.007)]. No statistically significant differences between the placebo and 800 mg clodronate groups were found in the femoral
neck BMD. In the primary study the urinary excretion of type I collagen aminoterminal telopeptide (NTX) decreased by 44% (p<0.0001 compared with placebo) and that of deoxypyridinoline by 18% (p<0.0001) in the clodronate 800 mg group. In the extension study urinary NTX decreased by 51% (p<0.0001) in those who were switched to 800 mg of clodronate and increased by 67% (p<0.0001) in those who stopped using that dose. There was no difference in the frequency of gastrointestinal complaints between
clodronate- and placebo-treated patients in the primary study, but they were more common among women who received clodronate
in the extension phase. Clodronate in daily doses of 400–800 mg caused a slight elevation of aminotransferase levels, usually
within the reference range. In bone biopsies no defect in mineralization was found. In conclusion, clodronate in a daily dose
of 800 mg prevents early postmenopausal bone loss at the sites of the skeleton in which cancellous bone predominates. It effectively
reduces bone resorption and bone turnover rate. Antifracture efficacy of clodronate remains to be established by prospective,
placebo-controlled trials.
Received: 4 March 2002 / Accepted: 9 July 2002 相似文献
998.
999.
HLA-DR typing in identical twins with insulin-dependent diabetes: difference between concordant and discordant pairs 总被引:3,自引:0,他引:3
C Johnston D A Pyke A G Cudworth E Wolf 《British medical journal (Clinical research ed.)》1983,286(6361):253-255
A total of 106 pairs of identical twins, of whom 56 were concordant and 50 discordant for insulin-dependent diabetes, were typed for HLA-DR. In both the concordant and discordant groups there was a high prevalence of the antigens DR3 and DR4, a low prevalence of DR5 and DR7, and a virtual absence of DR2. The heterozygous phenotype DR3,DR4 was more prevalent in concordant than discordant pairs. This was therefore the first demonstration of a genetic difference between concordant and discordant identical twin pairs. These findings suggest that possession of both DR3 and DR4 antigens confers a greater genetic predisposition to insulin-dependent diabetes than does the possession of either antigen alone. 相似文献
1000.
Martha A. Warpehoski Paul J. Buscemi David C. Osborn Birdwell Finlayson Eugene P. Goldberg 《Calcified tissue international》1981,33(1):211-222
Summary The quantity of protein and carbohydrate comprising the matrix of calcium oxalate monohydrate (COM) renal stones was found
to decrease with distance from the surface of the stone. The average organic concentration of stones 3 to 30 mm in diameter
ranged from 5.7% at the surface to 2.7% at the core. This concentration gradient suggests matrix involvement in a “growth
front” on stone surfaces with migration of organic material from the “older” interior. The matrix distribution was not readily
correlated with density variations or with the presence of hydroxyapatite or calcium oxalate dihydrate. Surface matrix concentrations
were greater than amounts predicted by physical adsorption. Electron microscopy confirmed the presence of the organic-rich
surface layer and also suggested that increase in stone size occurs predominantly by crystal growth with microcrystal aggregates
as growth centers. 相似文献