全文获取类型
收费全文 | 15276篇 |
免费 | 985篇 |
国内免费 | 48篇 |
专业分类
耳鼻咽喉 | 127篇 |
儿科学 | 446篇 |
妇产科学 | 321篇 |
基础医学 | 2086篇 |
口腔科学 | 323篇 |
临床医学 | 1461篇 |
内科学 | 3737篇 |
皮肤病学 | 205篇 |
神经病学 | 1412篇 |
特种医学 | 466篇 |
外国民族医学 | 10篇 |
外科学 | 2128篇 |
综合类 | 146篇 |
一般理论 | 4篇 |
预防医学 | 1154篇 |
眼科学 | 327篇 |
药学 | 802篇 |
中国医学 | 39篇 |
肿瘤学 | 1115篇 |
出版年
2023年 | 108篇 |
2022年 | 261篇 |
2021年 | 554篇 |
2020年 | 298篇 |
2019年 | 433篇 |
2018年 | 501篇 |
2017年 | 351篇 |
2016年 | 338篇 |
2015年 | 375篇 |
2014年 | 549篇 |
2013年 | 745篇 |
2012年 | 1188篇 |
2011年 | 1119篇 |
2010年 | 684篇 |
2009年 | 510篇 |
2008年 | 870篇 |
2007年 | 915篇 |
2006年 | 779篇 |
2005年 | 814篇 |
2004年 | 729篇 |
2003年 | 566篇 |
2002年 | 599篇 |
2001年 | 253篇 |
2000年 | 173篇 |
1999年 | 184篇 |
1998年 | 103篇 |
1997年 | 98篇 |
1996年 | 89篇 |
1995年 | 95篇 |
1994年 | 76篇 |
1993年 | 61篇 |
1992年 | 147篇 |
1991年 | 108篇 |
1990年 | 116篇 |
1989年 | 103篇 |
1988年 | 108篇 |
1987年 | 90篇 |
1986年 | 99篇 |
1985年 | 104篇 |
1984年 | 81篇 |
1983年 | 92篇 |
1982年 | 57篇 |
1981年 | 45篇 |
1980年 | 45篇 |
1979年 | 74篇 |
1978年 | 47篇 |
1976年 | 50篇 |
1974年 | 54篇 |
1973年 | 42篇 |
1972年 | 47篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
71.
In chronic beryllium disease (CBD), a granulomatous lung disease characterized by hypersensitivity to beryllium salts (BE), BE challenge of bronchoalveolar lavage cells induces IFNgamma. Although nitric oxide (NO) is elevated in CBD airways, the effects of NO on CBD IFNgamma responses are unknown. Here we report that BE-stimulated IFNgamma production in CBD lavage cells was markedly reduced (74%) by the NO generator DETA NONOate. Investigation of IFNgamma-stimulatory cytokine involvement indicated that lavage cell IL-18 was significantly increased (fourfold) by BE and reduced (64%) by DETA NONOate but IL-12 was undetectable. IL-18 production was caspase-1-dependent but caspase 1 inhibition reduced IFNgamma only partially (43%). Specific antibody depletion of lavage cell IL-18 yielded marginal reduction (19%) of IFNgamma. Data are the first to show that: (1) BE stimulates IL-18 as well as IFNgamma in CBD; (2) BE cytokine responses are NO-sensitive; and (3) NO down-regulation of IFNgamma involves other sites in addition to IL-18. 相似文献
72.
Joseph Kapelushnik Dan Engelhard Jayesh Mehta Reuven Or Yuval Brandstetter Elie Picard Gabriel Cividalli Arnon Nagler 《Journal of medical virology》1995,46(2):169-171
A 6-month-old child with familial hemophagocytic lymphohistiocytosis (FHL) experienced early sequential pneumonia due to respiratory syncytial virus (RSV) and cytomegalovirus (CMV) following bone marrow transplantation (BMT). The patient was deficient in natural killer (NK) cell activity (as found frequently in patients with FHL), and this risk factor may have played a major role in the concomitant infection by the two viral pathogens. Rapid diagnostic methods for both viruses are essential and early specific treatment may serve to ameliorate RSV- and CMV-induced lung injury in these life-threatening infections. © 1995 Wiley-Liss, Inc. 相似文献
73.
Role of matrix metalloproteinases in failure to re-epithelialize after corneal injury. 总被引:4,自引:1,他引:4
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)
M. E. Fini W. C. Parks W. B. Rinehart M. T. Girard M. Matsubara J. R. Cook J. A. West-Mays P. M. Sadow R. E. Burgeson J. J. Jeffrey M. B. Raizman R. R. Krueger J. D. Zieske 《The American journal of pathology》1996,149(4):1287-1302
Delayed re-epithelialization of the cornea after injury usually precedes stromal ulceration. Previous findings using a rat thermal injury model suggested that re-epithelialization is impeded by products of resident corneal cells, which destroy adhesive structures at the basement membrane zone. In this study, we provide additional evidence for this concept. Failure to re-epithelialize was found to correlate with an increase in the amounts of gelatinolytic matrix metalloproteinases present in the rat cornea. One of these gelatinases, gelatinase B, is synthesized by the resident corneal cells, and inhibitions of its synthesis correlated with inhibition of basement membrane dissolution. The matrix metalloproteinases collagenase and stromelysin are also synthesized by resident corneal cells in thermally injured corneas of rabbits, but the timing of bulk enzyme synthesis correlated more closely with deposition of repair tissue in the stroma than with failure to re-epithelialize. Nevertheless, in human corneas with repair defects, gelatinase B and collagenase are synthesized by cells in the basal layer of the epithelium directly adjacent to the basement membrane, suggesting that both could participate in dissolution of this structure. Importantly, treatment of thermally injured corneas with a synthetic inhibitor of matrix metalloproteinases significantly improved basement membrane integrity. These data support the concept that over-expression of matrix metalloproteinases by resident corneal cells impedes re-epithelialization after some types of corneal injury. 相似文献
74.
75.
Stimulation of T-helper cell gamma interferon and immunoglobulin G responses specific for Babesia bovis rhoptry-associated protein 1 (RAP-1) or a RAP-1 protein lacking the carboxy-terminal repeat region is insufficient to provide protective immunity against virulent B. bovis challenge
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)
Norimine J Mosqueda J Suarez C Palmer GH McElwain TF Mbassa G Brown WC 《Infection and immunity》2003,71(9):5021-5032
Rhoptry-associated protein 1 (RAP-1) is a targeted vaccine antigen for Babesia bovis and Babesia bigemina infections of cattle. The 60-kDa B. bovis RAP-1 is recognized by antibodies and T lymphocytes from cattle that recovered from infection and were immune to subsequent challenge. Immunization with native or recombinant protein was reported to reduce parasitemias in challenged animals. We recently reported that the NT domain of B. bovis RAP-1 contained immunodominant T-cell epitopes, whereas the repeat-rich CT domain was less immunostimulatory for T lymphocytes from cattle immune to B. bovis. The present study was therefore designed to test the hypothesis that the NT region of RAP-1, used as a vaccine with interleukin-12 and RIBI (catalog no. R-730; RIBI Immunochem Research, Inc., Hamilton, Mont. [now Corixa, Seattle, Wash.]) adjuvant to induce a type 1 response, would prime calves for antibody and T-helper cell responses comparable to or greater than those induced by full-length RAP-1 containing the C-terminal repeats. Furthermore, a type 1 immune response to RAP-1 was hypothesized to induce protection against challenge. Following four inoculations of either recombinant full-length RAP-1 or RAP-1 NT protein, RAP-1-specific immunoglobulin G (IgG) titers, T-lymphocyte proliferation, and gamma interferon production were similar. Similar numbers of NT region peptides were recognized. However, in spite of the presence of strong RAP-1-specific IgG and CD4(+)-T-lymphocyte responses that were recalled upon challenge, neither antigen stimulated a protective immune response. We conclude that successful priming of calves with recombinant RAP-1 and adjuvants that elicit strong Th1 cell and IgG responses is insufficient to protect calves against virulent B. bovis challenge. 相似文献
76.
Epidemiological markers for epidemic strain and carrier isolates in an outbreak of nosocomial oxacillin-resistant Staphylococcus aureus. 总被引:1,自引:5,他引:1
下载免费PDF全文
![点击此处可从《Journal of clinical microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
A Bouvet J M Fournier A Audurier C Branger A Orsoni C Girard 《Journal of clinical microbiology》1990,28(6):1338-1341
An outbreak of nosocomial infections occurring in a postoperative intensive care unit was caused by a single strain of oxacillin-resistant Staphylococcus aureus. Six patients were infected, or colonized, by this strain, which was traced by using the following four epidemiological markers: antibiogram, bacteriophage type, capsular polysaccharide type, and esterase electrophoretic type. This strain was compared with S. aureus isolates obtained from the noses of 13 carriers from a group of 42 staff members. A good correlation in terms of phenotypic markers was found between the epidemic strain and a strain isolated from one carrier. Both exhibited the same pattern of multiple resistance as well as the same phage type, 77, capsular polysaccharide type, 5, and esterase electrophoretic type, 6. In contrast, an oxacillin-resistant strain, isolated from another carrier, differed from the epidemic strain by susceptibility to rifampin and by susceptibility to four additional bacteriophages. The other 11 strains isolated from carriers were susceptible to oxacillin and exhibited widely different phenotypes. These results confirm the interest of using several epidemiological markers to trace the spread of epidemic S. aureus strains and to delineate the carrier strains. 相似文献
77.
Fernando Gabriel Chirdo María Cristina Añón Carlos Alberto Fossati 《Food and Agricultural Immunology》1998,10(2):143-155
Optimization of three enzyme immunoassays of very high sensitivity using three antiprolamin monoclonal antibodies (MAbs) (13B4, 11C4 and 12A1) is presented here. These MAbs are specific for those prolamins toxic for coeliac patients, as determined by immunoblotting analysis. Biotinylated MAbs were used in two of the assays. In a competitive ELISA, the binding of each biotinylated MAb to a gliadin‐coated solid phase was inhibited by gliadin in the fluid phase. The best result was obtained using the biotinylated MAbl3B4 (detection limit: 20 ng ml?1). With regard to capture ELISA, we tested the performance of the three MAbs. In this sandwich ELISA, the MAb used for antigenic capture was the same as that used as secondary biotinylated antibody. The MAbl2Al had the best performance (detection limit: 1 ng ml?1). The use of biotin‐labelled gliadin in a quantitative immunoassay with a detection limit of 5 ng ml?1 is also reported. This assay involves an antigenic capture using the MAbl2Al followed by a competition between biotinylated and non‐biotinylated gliadin. We have found the use of the streptavidin‐biotin interaction as signal amplification system to be very useful. This technique, as far as we know, has not been previously reported for gliadin quantification. 相似文献
78.
Gabriel G. Altmann 《Developmental dynamics》1975,143(2):219-239
Adult male rats received 15 mg/kg cycloheximide and the subsequent morphological effects at three and six hours after injection were evaluated using histometry, light and electron microscopy, histological demonstration of terminal web and acid phosphatase, and radioautography with tritiated thymidine. Rapid atrophy of the villi took place, progressing from the villus tip by premature exfoliation of epithelial cells. The crypts also diminished by random exfoliation of many crypt cells and by partial or complete disintegration. Mitosis and epithelial cell migration were absent. By six hours, the area occupied by the villi and the crypts per unit length of histological section was decreased by about 70–90% in most of the small intestine but only by about 40–60% in the duodenum and the terminal ileum. In the upper half of the villi, the epithelium was strongly positive for acid phosphatase and contained large numbers of round bodies resembling primary lysosomes. In the lower half, the microvillous border and terminal web were found to be disrupted. Animals receiving only 5 mg/kg cycloheximide also showed the atrophy of villi and crypts, and the round bodies resembling lysosomes. Evidence from several sources has indicated that protein synthesis in normal villus epithelial cells subsides toward the villus tip and becomes minimal at exfoliation. At exfoliation, proteins responsible for epithelial cohesion probably fail because they are no longer replenished. Cycloheximide appears to accelerate this process. 相似文献
79.
Toxoplasma gondii prevents neuron degeneration by interferon-gamma-activated microglia in a mechanism involving inhibition of inducible nitric oxide synthase and transforming growth factor-beta1 production by infected microglia 总被引:2,自引:0,他引:2
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)
Rozenfeld C Martinez R Seabra S Sant'anna C Gonçalves JG Bozza M Moura-Neto V De Souza W 《The American journal of pathology》2005,167(4):1021-1031
Interferon (IFN)-gamma, the main cytokine responsible for immunological defense against Toxoplasma gondii, is essential in all infected tissues, including the central nervous system. However, IFN-gamma-activated microglia may cause tissue injury through production of toxic metabolites such as nitric oxide (NO), a potent inducer of central nervous system pathologies related to inflammatory neuronal disturbances. Despite potential NO toxicity, neurodegeneration is not commonly found during chronic T. gondii infection. In this study, we describe decreased NO production by IFN-gamma-activated microglial cells infected by T. gondii. This effect involved strong inhibition of iNOS expression in IFN-gamma-activated, infected microglia but not in uninfected neighboring cells. The inhibition of NO production and iNOS expression were parallel with recovery of neurite outgrowth when neurons were co-cultured with T. gondii-infected, IFN-gamma-activated microglia. In the presence of transforming growth factor (TGF)-beta1-neutralizing antibodies, the beneficial effect of the parasite on neurons was abrogated, and NO production reverted to levels similar to IFN-gamma-activated uninfected co-cultures. In addition, we observed Smad-2 nuclear translocation, a hallmark of TGF-beta1 downstream signaling, in infected microglial cultures, emphasizing an autocrine effect restricted to infected cells. Together, these data may explain a neuropreservation pattern observed during immunocompetent host infection that is dependent on T. gondii-triggered TGF-beta1 secretion by infected microglia. 相似文献
80.
The lipid A region of lipopolysaccharides from Rhizobiaceae activates bone marrow granulocytes from lipopolysaccharide-hyporesponsive C3H/HeJ and C57BL/10ScCr mice
下载免费PDF全文
![点击此处可从《Immunology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
We established in previous studies that the binding of Salmonella lipopolysaccharide (LPS) to constitutive receptors of low affinity triggers the expression of the inducible LPS-binding molecule CD14 in bone marrow cells (BMC) of C3H/HeOU mice, but not in BMC from C3H/HeJ mice. We show in this study that BMC from C3H/HeJ and C57BL/10ScCr mice do not express CD14 after exposure to LPSs from Salmonella enterica and Bordetella pertussis, but do express this marker when treated with several LPSs from Rhizobiaceae, or their lipid A fragments. This shows that the constitutive LPS receptor in BMC from C3H/HeJ and C57BL/10ScCr mice is fully able to trigger a complete signalling cascade. Results of cross-inhibition of the binding of radiolabelled LPS indicated that active LPSs (from R. species Sin-1 and R. galegae) and inactive LPSs (from S. enterica and B. pertussis) bind to the same site of the constitutive LPS receptor of C3H/HeJ cells. Furthermore, binding of R. species Sin-1 LPS, and signalling induced by this LPS, were both inhibited by pre-exposure of C3H/HeJ cells to B. pertussis lipid A. This correlation between binding and signalling suggests that in C3H/HeJ cells, the constitutive receptor, which recognizes a large panel of LPSs from different origins, appears selectively unable to be activated by some particular LPSs, such as those of Enterobacteria and Bordetella. 相似文献