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11.
Connective tissue growth factor expression and Smad signaling during mouse heart development and myocardial infarction. 总被引:5,自引:0,他引:5
Susana M Chuva de Sousa Lopes Alie Feijen Jeroen Korving Olexander Korchynskyi Jonas Larsson Stefan Karlsson Peter ten Dijke Karen M Lyons Roel Goldschmeding Pieter Doevendans Christine L Mummery 《Developmental dynamics》2004,231(3):542-550
Connective tissue growth factor (CTGF) is reported to be a target gene of transforming growth factor beta (TGFbeta) and bone morphogenetic protein (BMP) in vitro. Its physiological role in angiogenesis and skeletogenesis during mouse development has been described recently. Here, we have mapped expression of CTGF mRNA during mouse heart development, postnatal adult life, and after experimental myocardial infarction. Furthermore, we investigated the relationship between CTGF and the BMP/TGFbeta signaling pathway in particular during heart development in mutant mice. Postnatally, CTGF expression in the heart became restricted to the atrium. Strikingly, 1 week after myocardial infarction, when myocytes have disappeared from the infarct zone, CTGF and TGFbeta expression as well as activated forms of TGFbeta but not BMP, Smad effector proteins are colocalized exclusively in the fibroblasts of the scar tissue, suggesting possible cooperation between CTGF and TGFbeta during the pathological fibrotic response. 相似文献
12.
Amaral IF Lamghari M Sousa SR Sampaio P Barbosa MA 《Journal of biomedical materials research. Part A》2005,75(2):387-397
Cell adhesion, migration, and proliferation of a few anchorage-dependent cells cultured on chitosan (Ch) matrices are influenced by the degree of N-acetylation (DA) of Ch. In the present work, we examined the influence of the DA on the attachment, spreading, proliferation, and osteogenic differentiation of rat bone marrow stromal cells (rBMSCs). Ch membranes were characterized in terms of surface morphology, roughness, and wettability, and in terms of adsorption of an adhesive protein, fibronectin (Fn). Chs with DAs in the range of 4 to 49% were used. Among the Ch samples, the DA of 4% led to the highest Fn surface concentration, both from single protein solution and from diluted serum. Furthermore, the levels of Fn adsorbed from serum found for this DA were threefold higher than for the tissue culture polystyrene control, indicating that in the presence of competitive proteins Ch is more specific toward Fn adsorption than tissue culture polystyrene. rBMSCs cultured on Ch carrying a DA of 4% were able to spread, proliferate, and differentiate, reaching a higher level of osteogenic differentiation than on the control, despite the lower cell attachment observed for all Ch samples. Because the Ch sample with a DA of 4% showed the highest Fn adsorption from serum, we suggest that cell adhesion, spreading, and osteogenic differentiation of rBMSCs on Ch may be mediated by the adsorbed layer of Fn. 相似文献
13.
Data emerging from recent in vivo and in vitro studies are pointing to basement membrane and other extra cellular matrix (ECM) components as likely determinants of specific lymphocyte entry and positioning in lymphoid tissues. In this report, the relevance of this notion is investigated in T-cell deficient (B) rat recipients of cardiac allografts, using an anti-laminin (LN) antibody as the probe. The 6-hr migration patterns of 111In-labelled peripheral lymph node (PLN) cells were followed in groups of engrafted B hosts treated with rabbit anti-rat LN antibody or rabbit serum. The accumulation of adoptively transferred cells in PLN and cardiac allografts of recipients pretreated with anti-LN antibody was significantly decreased compared to controls (P less than 0.05 and P less than 0.001, respectively). The transferred cells also localized in slightly lower numbers in the spleens and lungs of anti-LN conditioned rats; no differences were seen in the clearance of lymphocytes from peripheral blood, or their sequestration in liver and kidney. These data provide the first in vivo evidence that an antibody against LN selectively affects lymphocyte traffic. The results reinforce the notion that basement membrane components could be critical in 'directing' lymphocyte migration in vivo. 相似文献
14.
C1-esterase inhibitor blocks T lymphocyte proliferation and cytotoxic T lymphocyte generation in vitro 总被引:1,自引:0,他引:1
We have previously shown that activated C1s complement and activated T
cells cleave beta2-microglobulin (beta2m) in vitro leading to the formation
of desLys58 beta2m. This process can specifically be inhibited by
C1-esterase inhibitor (C1-inh). Furthermore we showed that exogenously
added desLys58 beta2m in nanomolar amounts to a one-way allogenic mixed
lymphocyte culture (MLC) increased the endogenous production of IL-2 and
the generation of allo-specific cytotoxic T lymphocytes. C1-inh was
purified from fresh human plasma and added to human or murine MLC and
mitogen-stimulated lymphocyte cultures grown in the presence of
complement-inactivated serum. Read-outs were cell proliferation, lymphokine
production and development of T cell-mediated cytotoxicity. We found that
addition of C1-inh to MLC and mitogen- exposed murine and human lymphocyte
cultures inhibited proliferation, the development of allospecific cytotoxic
activity, and changed the endogenous production of IL-2, IL-4, IL-10, IL-12
and IFN-gamma. These data clearly demonstrate a regulatory function of
C1-inh on T cell- mediated immune functions.
相似文献
15.
Dendritic cells (DCs) can be activated directly by triggering of receptors for pathogens or, indirectly, by exposure to inflammatory signals. It remains unclear, however, whether the two pathways result in qualitatively similar DCs or lead to equivalent adaptive immune responses. Here we report that indirect activation by inflammatory mediators generated DCs that supported CD4(+) T cell clonal expansion but failed to direct T helper cell differentiation. In contrast, exposure to pathogen components resulted in fully activated DCs that promoted T helper responses. These results indicate that inflammation cannot substitute for contact with pathogen components in DC activation and suggest that the function of pattern recognition by DCs is to couple the quality of the adaptive immune response to the nature of the pathogen. 相似文献
16.
Human mini-chromosomes in mouse embryonal stem cells 总被引:3,自引:2,他引:3
We have introduced human mini-chromosomes of 4 Mb and approximately 15 Mb
in size into mouse embryonal stem cells. Although these human mini-
chromosomes are stable in hamster and chicken cells, they re-arrange or
segregate aberrantly in the embryonal stem cells and are rapidly lost in
the absence of selection. However, one of the mini-chromosomes re-
arranged, acquired mouse centromeric sequences and was then stably
maintained for at least 60 population doublings in culture. This mini-
chromosome, which is 4 Mb in size, is a candidate for a mouse germ line
chromosome vector.
相似文献
17.
Determination of the parent of origin in nine cases of prenatally detected chromosome aberrations found after intracytoplasmic sperm injection 总被引:1,自引:17,他引:1
Van Opstal D; Los FJ; Ramlakhan S; Van Hemel JO; Van Den Ouweland AM; Brandenburg H; Pieters MH; Verhoeff A; Vermeer MC; Dhont M; In't Veld PA 《Human reproduction (Oxford, England)》1997,12(4):682-686
Prenatal cytogenetic analysis of 71 fetuses conceived by intracytoplasmic
sperm injection (ICSI) resulted in the detection of nine (12.7%) chromosome
aberrations including two cases of 47,XXY, four cases involving a 45,X cell
line and three autosomal trisomies. Molecular analysis of the parental
origin of the deleted or supernumerary chromosome was performed by using
polymorphic microsatellite markers. Six cases involving a sex chromosome
abnormality were found to be of paternal origin while the two trisomic
cases that could be analysed were of maternal origin. Two cases involved
the same infertile couple who had two consecutive ICSI pregnancies
terminated because of a chromosome abnormality. The replaced embryos in
both cases originated from a single batch of ICSI fertilized oocytes of
which part was used to initiate the first pregnancy and part was
cryopreserved and used to initiate the second pregnancy.
相似文献
18.
Developmental changes in calcium dynamics, protein kinase C distribution and endoplasmic reticulum organization in human preimplantation embryos 总被引:2,自引:2,他引:2
Developmental changes in the Ca2+ dynamics of human zygotesand preimplantation embryos were related to changes in the distributionof endoplasmic reticulum (ER) and protein kinase C (PKC). Thefertilization-induced Ca2+ oscillations were typically observedover >5 h, were ryanodine-sensitive and showed a periphery-to-centrepropagation of Ca2+ waves. At the same time, ER and PKC wereaccumulated in the cell periphery. After the appearance of pronuclei,ryanodine-sensitive Ca2+ oscillations of lower amplitude andfrequency were observed until the pronuclear breakdown. However,Ca2+ waves then began in the perinuclear region, in the areaof ER and PKC accumulation and spread towards the cell periphery.During the second to fourth cell cycle, small sinusoidal Ca2+fluctuations were observed; sparse higher-amplitude Ca2+ spikes,superimposed on these basal fluctuations, appeared shortly beforecell division. The sinusoidal Ca2+ fluctuations were asynchronousin individual blastomeres and disappeared progressively in arrestedembryos. The direction of Ca2+ wave propagation and the distributionof ER and PKC were similar to the situation observed in pronuclearzygotes. In contrast to the zygotes, ryanodine did not arrestthe Ca2+ oscillations but augmented their amplitude and frequency.These data suggest that human pre-embryos use different mechanismsof Ca2+ signalling in the early post-fertilization period, duringthe pronuclear development and during cleavage. calcium dynamics/endoplasmic reticulum/human preimplantation embryos/protein kinase C/ryanodine 相似文献
19.
Glucocorticoid resistance in asthma is associated with elevated in vivo expression of the glucocorticoid receptor beta-isoform 总被引:18,自引:0,他引:18
Sousa AR Lane SJ Cidlowski JA Staynov DZ Lee TH 《The Journal of allergy and clinical immunology》2000,105(5):943-950
BACKGROUND: Glucocorticoid-resistant bronchial asthma is characterized by failure of corticosteroids to suppress key asthma-relevant, cell-mediated inflammatory responses in the airways. OBJECTIVE: The mechanism of this phenomenon is not clear but may involve aberrant expression of the beta-isoform of the glucocorticoid receptor. METHODS: We have measured expression of the alpha- and beta-glucocorticoid receptor isoforms in tuberculin-driven cutaneous cell-mediated inflammatory lesions in people with asthma who are glucocorticoid sensitive and resistant after 9 days of therapy with oral prednisolone (40 mg/day) or matching placebo in a random order, crossover design. RESULTS: After placebo therapy, the mean numbers of cells expressing glucocorticoid receptor alpha immunoreactivity in the lesions evoked in glucocorticoid-sensitive and -resistant patients with asthma were statistically equivalent. The numbers of cells expressing glucocorticoid receptor beta were significantly elevated in the patients who were glucocorticoid resistant, resulting in an 8-fold higher ratio of expression of glucocorticoid receptor alpha/glucocorticoid receptor beta in the patients who were glucocorticoid sensitive. Glucocorticoid receptor alpha/glucocorticoid receptors beta were colocalized to the same cells. Oral prednisolone therapy was associated with a significant decrease in the numbers of cells expressing glucocorticoid receptor alpha but not glucocorticoid receptor beta in the subjects who were glucocorticoid sensitive. No significant change was found in the numbers of cells expressing glucocorticoid receptor alpha and glucocorticoid receptor beta in the patients who were glucocorticoid resistant. Prednisolone therapy reduced the ratio of glucocorticoid receptor alpha/glucocorticoid receptor beta expression for the patients who were glucocorticoid sensitive to a level seen in the patients who were glucocorticoid resistant before therapy. CONCLUSION: Because glucocorticoid receptor beta inhibits alpha-glucocorticoid receptor-mediated transactivation of target genes, the increased expression of glucocorticoid receptor beta in inflammatory cells might be a critical mechanism for conferring glucocorticoid resistance. 相似文献
20.
No Abstract 相似文献