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41.
Liñares D Mañá P Goodyear M Chow AM Clavarino C Huntington ND Barnett L Koentgen F Tomioka R Bernard CC Freire-Garabal M Reid HH 《Journal of autoimmunity》2003,21(4):339-351
Myelin oligodendrocyte glycoprotein (MOG) is a minor component of central nervous system myelin presumably implicated in the pathogenesis of Multiple Sclerosis (MS). Immunization with MOG leads to the development of Experimental Autoimmune Encephalomyelitis (EAE), the experimental model of MS. It has been suggested that its encephalitogenic potential may be due to the lack of MOG self-immune tolerance. To clarify this, we have generated a MOG deficient mouse (MOG(-/-)) strain. Surprisingly, MOG(35-55)specific proliferation and Th1-type cytokine production were markedly enhanced in MOG(-/-)mice compared to wild type control. Furthermore, adoptive transfer of MOG(35-55)specific T cells, isolated from MOG deficient mice, into wild-type recipients resulted in the development of a more severe disease, indicating a high capacity of MOG(-/-)T cells to initiate effector responses. Interestingly, T cell reactivity to overlapping MOG peptides in MOG(-/-)mice did not reveal new potential immunodominant epitopes in H-2(b)mice. Taken together, our data suggests that MOG self-tolerance modulates the encephalitogenic potential of autoreactive MOG T cells in the periphery. 相似文献
42.
Novel proteins with binding specificity for DNA CTG repeats and RNA CUG repeats: implications for myotonic dystrophy 总被引:7,自引:6,他引:7
While an unstable CTG triplet repeat expansion is responsible for myotonic
dystrophy, the mechanism whereby this genetic defect induces the disease
remains unknown. To detect proteins binding to CTG triplet repeats, we
performed bandshift analysis using as probes double- stranded DNA fragments
having CTG repeats [ds(CTG)6-10] and single- stranded oligonucleotides
having CTG repeats ss(CTG)8 or RNA CUG triplet repeats (CUG)8. The source
of protein was nuclear and cytoplasmic extracts of HeLa cells, fibroblasts
and myotubes. Proteins binding to the double-stranded DNA repeat
[ds(CTG)6-10], were inhibited by nonlabeled ds(CTG)6-10, but not by a
non-specific DNA fragment (USF/AD-ML). Another protein binding to ssCTG
probe and RNA CUG probe was inhibited by nonlabeled (CTG)8 and (CUG)8.
Nonlabeled oligos with different triplet repeat sequences, ss(CAG)8 or
ss(CGG)8, did not inhibit binding to the ss(CTG)8 probe. However, when
labeled as probes, the (CAG)8 and (CGG)8 bound to proteins distinct from
the CTG proteins and binding was inhibited by nonlabeled (CAG)8 or (CGG)8
respectively. The protein binding only to the RNA repeat (CUG)8 was
inhibited by nonlabeled (CUG)8 but not by nonlabeled single- or
double-stranded CTG repeats. Furthermore, the CUG-BP exhibited no binding
to an RNA oligonucleotide of triplet repeats of the same length but having
a different sequence, CGG. The CUG binding protein was localized to the
cytoplasm, whereas dsDNA binding proteins were localized to the nuclear
extract. Thus, several trinucleotide binding proteins exist and their
specificity is determined by the triplet sequence. The novel protein,
CUG-BP, is particularly interesting since it binds to triplet repeats known
to be present in myotonin protein kinase mRNA which is responsible for
myotonic dystrophy.
相似文献
43.
Nash LG Phillips MN Nicholson H Barnett R Zhang M 《Clinical anatomy (New York, N.Y.)》2004,17(4):287-293
Skin ligaments (SL) (L. retinacula cutis) are present extensively in the face, hands, feet, and in breast tissue, but have seldom been reported elsewhere in the body. The traditional histological view of the subcutaneous region is that it comprises a matrix of loose connective tissue devoid of fibrous specializations. The purpose of this study was to determine the structure and distribution of skin ligaments. Eight embalmed cadavers (3 males, 5 females, 69-90 years of age) were used in this study. Tissue was prepared using the E12 plastination technique. Macroscopic and microscopic examination demonstrated the widespread presence in the limbs and most of the rest of the body of fibrous strands linking the base of the dermis and the superficial fibers of the underlying deep fascia. The morphology and distribution of these skin ligaments were similar in the individuals examined. Variations in the structure of the skin ligaments depended on the presence of underlying muscle, neurovascular bundles, intermuscular septa and adipose tissue. We conclude that skin ligaments are complex fibrous structures that are present over most of the body. They form an extensive peripheral network in the subcutaneous fat. These 'ligaments' seem to provide an anchorage of skin to deep fascia that is flexible and yet resistant to mechanical loading from multi-directional forces. The use of the E12 plastination technique coupled with fluorescent confocal microscopy has been of benefit in visualizing and delineating SLs from other soft tissue structures in three planes. 相似文献
44.
Bersinger NA; Brandenberger A; Berger E; Baumann CK; Birkhauser MH 《Human reproduction (Oxford, England)》1998,13(7):1962-1967
We have previously observed the repeated presence of low but detectable
amounts of the trophoblast marker pregnancy-specific beta1-glycoprotein
(SP1) in the serum of some women undergoing in-vitro fertilization (IVF)
treatment around the time of oocyte retrieval. The occurrence of these
signals seemed to be restricted to a defined group of patients which also
showed a lower pregnancy success rate in a preliminary study. To test our
hypothesis we have analysed 173 consecutive cycles leading to an embryo
transfer. Fifty-four cycles (31%) had a serum SP1 level of at least 0.1
ng/ml between days embryo transfer -5 and embryo transfer (group A). Five
pregnancies were obtained in this group (pregnancy rate = 9.3%), while in
group B, defined by the absence of detectable SP1 before embryo transfer
(119 cycles), 36 ongoing pregnancies were achieved (30.3%). Ten of the 41
pregnancies were achieved in 33 first-time non-pregnant patients undergoing
further attempts during the study period. Again the pregnancy rate was
higher in the first-time group B women (9/23 versus 1/10 for group A).
Patients tended to remain in their groups A or B, the latter being
associated with a better immediate as well as subsequent chance for
pregnancy. Group A cycles had a significantly lower endometrial thickness
two days before oocyte retrieval than group B (P = 0.0011). We postulate
that the presence of an unknown, maternal and progesterone- or follicle
stimulating hormone-independent factor in some patients could stimulate
tonic ectopic SP1 synthesis and at the same time negatively influence
endometrial development.
相似文献
45.
Leigh A Compton Dru A Potash Nathan A Mundell Joey V Barnett 《Developmental dynamics》2006,235(1):82-93
During embryogenesis, epicardial cells undergo epithelial-mesenchymal transformation (EMT), invade the myocardium, and differentiate into components of the coronary vasculature, including smooth muscle cells. We tested the hypothesis that transforming growth factor-beta (TGFbeta) stimulates EMT and smooth muscle differentiation of epicardial cells. In epicardial explants, TGFbeta1 and TGFbeta2 induce loss of epithelial morphology, cytokeratin, and membrane-associated Zonula Occludens-1 and increase the smooth muscle markers calponin and caldesmon. Inhibition of activin receptor-like kinase (ALK) 5 blocks these effects, whereas constitutively active (ca) ALK5 increases cell invasion by 42%. Overexpression of Smad 3 did not mimic the effects of caALK5. Inhibition of p160 rho kinase or p38 MAP kinase prevented the loss of epithelial morphology in response to TGFbeta, whereas only inhibition of p160 rho kinase blocked TGFbeta-stimulated caldesmon expression. These data demonstrate that TGFbeta stimulates loss of epithelial character and smooth muscle differentiation in epicardial cells by means of a mechanism that requires ALK5 and p160 rho kinase. 相似文献
46.
Serological heterogeneity of the IgM components of mixed (monoclonal IgM–polyclonal IgG) cryoglobulins
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M. R. Mackenzie L. S. Goldberg E. V. Barnett H. H. Fudenberg 《Clinical and experimental immunology》1968,3(9):931-941
Mixed IgG–IgM cryoglobulins were isolated from the sera of seven patients with macroglobulinaemia or cryoglobulinaemia. The IgM components of all seven cryoproteins were monoclonal, containing κ light chains only, whereas the IgG components were polyclonal, containing both κ and λ light chains. Despite their apparent immunological homogeneity, the IgM components showed a wide range of antiglobulin activity. The data indicate that serological specificity may vary from one mixed cryoglobulin to another and that the monoclonal IgM components of different mixed cryoglobulins represent a heterologous group of antiglobulins. 相似文献
47.
Precipitating antibodies to DNA induced by heat-denatured DNA-albumin conjugates in the rabbit 总被引:1,自引:0,他引:1
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(1) Antibodies reactive with purified DNA in the complement fixation system and induced by active immunization of rabbits with methylated bovine serum albumin—DNA aggregate (MBSA—DNA) have been previously described. The present study demonstrates their reactivity in the quantitative and double diffusion preciptin systems. In these systems they have shown preferential reactivity with heat denatured DNA and great cross-reactivity with denatured DNA from various sources.
(2) Methylated rabbit serum albumin—DNA aggregate (MRSA—DNA) is an effective immunizing antigen resulting in the production of antibodies similar to those produced by MBSA—DNA.
(3) The precipitating antibodies in this system are 19S immunoglobulins and appear to be identical to the complement fixing antibodies.
(4) The precipitin reaction is not significantly inhibited by mono-nucleotides.
相似文献48.
The infectivity of a bovine rotavirus was enhanced 140-, 8-, and 3-fold, respectively, by trypsin, protease, and lactase. Ficin, carboxypeptidases A and B, lysozyme, and beta-galactosidase had little effect on the infectivity. Chymotrypsin caused a threefold decrease in the infectivity. Trypsin acts directly on the rotavirus and not on the host cell. 相似文献
49.
Evaluation of fluorescent antinuclear antibody assays, Crithidia luciliae substrate, and single-stranded DNA-binding capacity in diagnosis of four rheumatic diseases.
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Sera from groups of patient with systemic lupus erythematosus, mixed connective tissue disease, rheumatoid arthritis, and progressive systemic sclerosis and normal controls were compared, using different antinuclear antibody assays. Hep-II cells, used as a substrate for the detection of antinuclear antibodies, appeared to be more sensitive than rat liver substrate. In addition, the fluorescent patterns were easier to identify on Hep-II cells. All systemic lupus erythematosus sera with antibodies reactive with kinetoplasts of Crithidia luciliae had binding greater than 43% for single-stranded DNA. Based on the high sensitivity of the Hep-II substrate and the relative specificity of high (greater than 43%) binding for single stranded DNA by sera from patients with systemic lupus erythematosus, it appears that these two tests are most useful in differential diagnosis and for the detection of systemic lupus erythematosus. 相似文献
50.
Lymphocyte subpopulations in patients with hydroxocobalamin responsive megaloblastic anaemia. 总被引:1,自引:2,他引:1
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Lymphocyte subpopulations and intrinsic factor and gastric parietal cell antibodies have been measured in 23 patients with megaloblastic anaemia who responded to treatment with hydroxocobalamin. The ratio of helper (OKT4) to suppressor (OKT8) lymphocytes was significantly increased in patients with intrinsic factor antibody compared with those who lacked the antibody. No such correlation was found for gastric parietal cell antibody. Alterations in the lymphocyte helper to suppressor (OKT4:OKT8) ratio may be associated with pernicious anaemia. 相似文献