全文获取类型
收费全文 | 6682篇 |
免费 | 603篇 |
国内免费 | 11篇 |
专业分类
耳鼻咽喉 | 62篇 |
儿科学 | 171篇 |
妇产科学 | 294篇 |
基础医学 | 885篇 |
口腔科学 | 50篇 |
临床医学 | 1024篇 |
内科学 | 1027篇 |
皮肤病学 | 168篇 |
神经病学 | 506篇 |
特种医学 | 136篇 |
外国民族医学 | 1篇 |
外科学 | 837篇 |
综合类 | 151篇 |
一般理论 | 12篇 |
预防医学 | 822篇 |
眼科学 | 55篇 |
药学 | 592篇 |
中国医学 | 7篇 |
肿瘤学 | 496篇 |
出版年
2023年 | 23篇 |
2022年 | 50篇 |
2021年 | 109篇 |
2020年 | 56篇 |
2019年 | 115篇 |
2018年 | 136篇 |
2017年 | 106篇 |
2016年 | 138篇 |
2015年 | 143篇 |
2014年 | 209篇 |
2013年 | 326篇 |
2012年 | 473篇 |
2011年 | 458篇 |
2010年 | 280篇 |
2009年 | 244篇 |
2008年 | 442篇 |
2007年 | 434篇 |
2006年 | 405篇 |
2005年 | 393篇 |
2004年 | 390篇 |
2003年 | 336篇 |
2002年 | 306篇 |
2001年 | 145篇 |
2000年 | 97篇 |
1999年 | 108篇 |
1998年 | 66篇 |
1997年 | 54篇 |
1996年 | 55篇 |
1995年 | 62篇 |
1994年 | 40篇 |
1993年 | 51篇 |
1992年 | 101篇 |
1991年 | 84篇 |
1990年 | 62篇 |
1989年 | 80篇 |
1988年 | 57篇 |
1987年 | 51篇 |
1986年 | 42篇 |
1985年 | 61篇 |
1984年 | 64篇 |
1983年 | 46篇 |
1982年 | 35篇 |
1981年 | 30篇 |
1980年 | 26篇 |
1979年 | 35篇 |
1978年 | 24篇 |
1977年 | 23篇 |
1976年 | 19篇 |
1974年 | 26篇 |
1973年 | 23篇 |
排序方式: 共有7296条查询结果,搜索用时 22 毫秒
51.
52.
McGregor DH Yang Q Fan F Talley RL Topalovski M 《Annals of clinical and laboratory science》2001,31(1):103-107
Scabies, infection with Sarcoptes scabiei, is known to be predisposed to by poor body hygiene, environmental exposure, and systemic immunodeficiency. We report the case of an 83-year-old man with Sezary's syndrome who developed scabies limited to the skin of the upper chest, the same location where he had previously received electron beam radiation treatments for cutaneous T-cell lymphoma. Histologic and immunohistochemical studies demonstrated that sections of the previously irradiated right and left chest skin, compared to non-irradiated chest, abdominal, and leg skin, had infestation by scabies, diminished involvement by T-cell lymphoma, and notably reduced numbers of Langerhans cells. These findings suggest that the development of scabies may be predisposed to by local cutaneous radiation therapy, and that it may be mediated by local cutaneous immunodeficiency secondary to reduced numbers of Langerhans cells. 相似文献
53.
Dekker C Uthaipibull C Calder LJ Lock M Grainger M Morgan WD Dodson GG Holder AA 《Molecular and biochemical parasitology》2004,137(1):143-149
Blood-stage malaria vaccine candidates include surface proteins of the merozoite. Antibodies to these proteins may either block essential steps during invasion or render the merozoite susceptible to phagocytosis or complement-mediated degradation. Structural information on merozoite surface proteins complexed to antibodies provides crucial information for knowledge-based vaccine design. The major merozoite surface protein MSP1 is an abundant surface molecule in Plasmodium falciparum. Only a subset of antibodies against MSP119 inhibits invasion (inhibitory antibodies), whereas other antibodies binding to MSP119 have no effect on invasion (neutral antibodies). Here we report on the complex of MSP119 with both inhibitory monoclonal antibody 12.10 and neutral monoclonal antibody 2F10. The complexes were established using both whole IgG's and Fab fragments, and analysed by dynamic light scattering, electron microscopy and analytical ultra centrifugation. Specific ring structures were formed in the ternary complex with the two antibodies, providing direct evidence of non-overlapping epitopes on MSP119. Mutational studies also indicated that the epitopes of the inhibitory and neutral antibodies are spatially remote. 相似文献
54.
Settmacher B Rheinheimer C Hamacher H Ames RS Wise A Jenkinson L Bock D Schaefer M Köhl J Klos A 《European journal of immunology》2003,33(4):920-927
The anaphylatoxic peptide C3a is a pro-inflammatory mediator generated during complement activation, whose specific G protein coupled receptor is expressed on granulocytes, monocytes, mast cells, activated lymphocytes, and in the nervous tissue. We have generated RBL-2H3 cell clones stably expressing mutants of the human C3a-receptor (C3aR) with combined alanine (Ala) substitutions of ten C-terminal serine (Ser) or threonine (Thr) residues, which may represent putative phosphorylation sites to characterize their role in ligand-induced C3aR internalization and signaling. Ser475/479 and Thr480/481 as well as Ser449 seemed not to be involved in ligand-induced receptor internalization. Either directly or by a conformational change they even "inhibit" C3aR internalization. In contrast, mutants with Ala substitutions at Ser465/470 and Thr463/466 were poorly internalized, and Thr463 seemed to be the most important C-terminal Thr or Ser residue directly effecting receptor internalization. However, it is likely that other C3aR regions additionally participate in this negative feed-back mechanism since even mutants with multiple Ala substitutions still internalized to a limited degree. Interestingly, in a mutant with a single exchange of Ser449 to Ala, the signal transduction assessed by a Ca(2+) assay and [(35)S]GTP gamma S-binding on HEK cells transiently co-transfected with G-alpha 16 or G-alpha O, respectively, was severely impaired, indicating that this residue of C3aR is involved in G protein coupling. 相似文献
55.
56.
CD44 can function as a receptor for hyaluronan (HA). However, many cell lines and normal hematopoietic cells that express CD44 do not constitutively bind HA. A monoclonal antibody (mAb) specific for CD44 (IRAWB14) has been described previously which induces CD44-mediated binding of HA rapidly (seconds to minutes) in some cell lines and in normal murine T cells. Of 16 CD44-specific mAb tested in the present study, only 3 exhibited this activity. Monovalent Fab fragments were prepared from two IgG2a antibodies that induce HA binding (IRAWB 14 and IRAWB 26) and used to determine whether multivalent binding was required for induction of HA receptor function. Fab from both antibodies had a tendency to form multivalent aggregates. After addition of iodoacetamide to prevent further aggregation, multimeric and monovalent forms were separated by gel filtration. This made it possible to compare the inducing activity of monovalent and multivalent antibody fragments of identical composition in the absence of Fc determinants. Multimeric forms were very active at inducing binding of fluorescein-conjugated HA (Fl-HA). Monovalent Fab fragments of both antibodies had 20- to 50-fold lower binding activity than intact antibody or multimer. IRAWB 26 Fab monomers were completely inactive in the induction of HA-binding. The observed weak inducing activity of IRAWB 14 Fab monomer could be attributed to very low levels of contaminating multimer. Induction of HA binding could also be achieved by using anti-immunoglobulin to cross-link Fab monomers of IRAWB 26. Thus, multivalent binding was required for the activation of HA binding by CD44-specific antibody, suggesting that the distribution of CD44 molecules on the cell surface is important for HA receptor function. In kinetic studies, induction of HA receptor function occurred simultaneously with antibody binding at 0°C (ice water bath). Furthermore, antibody could induce HA binding in paraformaldehyde-fixed cells, which were permeable to propidium iodide and trypan blue, suggesting that intracellular signaling mechanisms were not involved in induction of receptor function. We conclude, therefore, that these CD44-specific antibodies are inducing HA binding by directly influencing the distribution of CD44 on the cell surface. The possibility of a concurrent change in CD44 conformation is not ruled out. We discuss possible mechanisms by which CD44 might be activated to bind HA in vivo. 相似文献
57.
58.
Unaltered thyroid function in mice responding to a highly immunogenic thyrotropin receptor: implications for the establishment of a mouse model for Graves' disease. 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Clinical and experimental immunology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
G Carayanniotis G C Huang L B Nicholson T Scott P Allain A M McGregor J P Banga 《Clinical and experimental immunology》1995,99(2):294-302
Grave's disease (GD) is a common disorder characterized by the presence of autoantibodies to the thyrotropin receptor. In the past, the exceedingly low expression of the thyrotropin receptor on thyrocytes has not allowed its purification in quantities sufficient to investigate the establishment of an animal model for this disease. In this study, we have purified the 398-amino acid, extracellular region of the human thyrotropin receptor (TSH-R.E) from insect cells using recombinant baculovirus, and explored its immunopathogenic properties in H-2b,d,q,k,s strains of mice. The receptor preparation was highly immunogenic since it elicited strong specific proliferative T cell responses as well as IgG responses in all strains tested. In addition, hyperimmunization with TSH-R.E induced (i) serum antibodies that blocked the binding of 125I-TSH to its receptor, a common feature of GD autoantibodies; and (ii) IgG that reacted with a synthetic peptide (residues 32-54) from the N-terminus of the receptor, a region implicated in the binding of thyroid stimulating antibodies. In SJL animals only, a weak antibody response to two other thyroid antigens, thyroglobulin and thyroid peroxidase, was also observed. The presence of these antibodies, however, was not accompanied by a detectable alteration in thyroid function as assessed by the measurement of serum TSH, T4 and iodine levels. Also mononuclear infiltration of the thyroid gland or morphological changes compatible with an activation state of thyrocytes were not apparent in TSH-R-challenged mice. In contrast, mice treated with the anti-oxidant aminotriazole showed a dramatic increase in serum TSH levels and an activated follicular epithelium. These data demonstrate that a highly immunogenic TSH-R.E in mice does not necessarily provide a proper stimulus for the induction of a hyper- or hypothyroid status as defined by hormonal or histological criteria. Main reasons for the inability to induce receptor-specific antibodies that affect thyroid function such as those generated in GD are likely to be the inappropriate folding of the recombinant extracellular domain of the receptor, or the xenogeneic nature of the autoantigen. 相似文献
59.
Smyth LA Ardouin L Williams O Norton T Tybulewicz V Kioussis D 《European journal of immunology》2002,32(12):3386-3394
Interactions of T cells with MHC plus peptide in the peripheral lymphoid system are important for their survival. In this study we investigated further the molecular consequences of such interactions using F5 TCR transgenic mice and peptides previously shown to induce either negative or positive selection in the thymus. Following TCR ligation with the negatively selecting agonist peptide, mature CD8(+) cells proliferated and up-regulated the activation marker CD69. Interestingly, ligation of this TCR with MHC molecules loaded with high concentrations of the positively selecting peptide also resulted in the aforementioned changes, but with slower kinetics. Analysis of the biochemical changes that occur following stimulation with these peptides showed that phosphorylation of key signaling molecules, such as ZAP-70, CD3zeta, Vav, SLP-76, LAT, and ERK-1 and 2, could be detected after exposure to agonist but not antagonist peptide. Confocal microscopy, however, revealed infrequent phosphorylation 'patches' at the site of contact between T cells and APC presenting the antagonist peptide. Our data suggest that peptides capable of inducing positive selection in the thymus can be recognized by mature T cells and cause proliferation, up-regulation of CD69 and accumulation of phosphorylated proteins at the immunological synapse with low efficiency; however no phosphorylation of signaling molecules can be detected using conventional biochemical assays. 相似文献
60.
Williams GC McGregor HA King D Nelson CC Glasgow RE 《Patient education and counseling》2005,57(1):39-45
There is considerable variation in care provided to patients with diabetes related to metabolic control, preventive services, and degree of patient-centered support. This study evaluates the relation of self-determination theory (SDT) constructs of clinician autonomy support, and patient competence to glycemic control, depressive symptoms, and patient satisfaction from baseline surveys of 634 patients of 31 Colorado primary care physicians participating in a program to improve diabetes care. Spearman correlations of autonomy support from one's clinician with patient competence, HbA1c, depressive symptoms and satisfaction were significant (R = -0.11 to 0.55, P < 0.005). Structural equation modeling demonstrated that autonomy support was significantly related to perceived competence, depressive symptoms, patient satisfaction, and indirectly to glycemic control. Perceived competence was significantly related to depressive symptoms, patient satisfaction and glycemic control. Further, the motivation constructs from SDT accounted for 5% of the variance in glycemic control, 8% of the variance in depression, and 42% of the variance in patient satisfaction. Quality improvement efforts need to pay greater attention to patient competence, satisfaction, and depression, in addition to glycemic control. Clinician autonomy support was found to be reliably measured and moderately correlated with psychosocial and biologic outcomes related to diabetes self-management. These results suggest training clinicians to increase their support of patient autonomy may be one important avenue to improve diabetes outcomes. 相似文献