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81.
Bernd Groner Astrid Weiss 《BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy》2014,28(1):27-39
Survivin is a well-established target in experimental cancer therapy. The molecule is over-expressed in most human tumors, but hardly detectable in normal tissues. Multiple functions in different subcellular compartments have been assigned. It participates in the control of cell division, apoptosis, the cellular stress response, and also in the regulation of cell migration and metastasis. Survivin expression has been recognized as a biomarker: high expression indicates an unfavorable prognosis and resistance to chemotherapeutic agents and radiation treatment. Survivin is an unconventional drug target and several indirect approaches have been exploited to affect its function and the phenotype of survivin-expressing cells. Interference with the expression of the survivin gene, the utilization of its messenger RNA, the intracellular localization, the interaction with binding partners, the stability of the survivin protein, and the induction of survivin-specific immune responses have been taken into consideration. A direct strategy to inhibit survivin has been based on the identification of a specifically interacting peptide. This peptide can recognize survivin intracellularly and cause the degradation of the ligand–survivin complex. Technology is being developed that might allow the derivation of small molecular-weight, drug-like compounds that are functionally equivalent to the peptide ligand. 相似文献
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83.
Membrane‐bound stem cell factor is the major but not only driver of fibroblast‐induced murine skin mast cell differentiation
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Mandy Leist Cathleen Annett Sünder Sebastian Drube Carolin Zimmermann Astrid Geldmacher Martin Metz Marcus Maurer 《Experimental dermatology》2017,26(3):255-262
The maintenance and modulation of cutaneous mast cell (MC) numbers is held to be important for skin immune responses to allergens and pathogens. The increase in MC numbers in the skin is achieved by proliferation and the differentiation of precursor to mature MCs. Fibroblast‐derived SCF is thought to be the major skin MC growth factor and it potently induces MC proliferation. The mechanisms of fibroblast‐induced skin MC differentiation, including the role of SCF, however, remain insufficiently characterized and understood. Using cocultures of immature murine MCs and fibroblasts, we found that the adhesion of immature MCs to fibroblasts via VCAM‐1 and α4β7 integrin is very important for subsequent differentiation, which is driven by fibroblast membrane‐bound SCF and additional fibroblast‐derived membrane‐bound signals. Thus, our results show that fibroblast‐induced MC differentiation is induced by direct cell–cell contact and involves both Kit‐dependent and Kit‐independent pathways. Our findings add to the understanding of how immature mast cells mature in murine skin and encourage further analyses of the underlying mechanisms, which may result in novel targets for the modulation of skin mast cell driven diseases. 相似文献
84.
Epidemiological study of paediatric germ cell tumours revealed the incidence and distribution that was expected,but a low mortality rate
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86.
ras and c-myc protein expression in colorectal carcinoma 总被引:6,自引:0,他引:6
Felice Miller M.D. Tomas M. Heimann M.D. Astrid Quish M.D. Daniel J. Pyo M.D. Arnold Szporn M.D. Giorgio Martinelli Ph.D. Thomas M. Fasy M.D. Ph.D. 《Diseases of the colon and rectum》1992,35(5):430-435
This study was performed to determine the correlation of tumor ras and c-myc oncogene expression with clinical and prognostic variables in patients prone to develop colorectal cancer. One hundred eighteen patients with colorectal cancer were studied; mean age was 40 years. Fifty-three were young patients (age 40 or less), 49 had ulcerative colitis, and 16 had multiple polyposis coli. Immunoperoxidase stains of paraffin-embedded cancer sections were performed for the c-myc and ras proteins. ras staining was found to correlate with Dukes stage and prognosis. Patients with tumors negative for ras protein stain had an actuarial five-year survival of 61 percent versus 44 percent for those tumors with a positive stain (P less than 0.05). This correlation was not seen with the c-myc stain. Positive ras oncogene stain appears to be a useful indicator of advanced stage and poor prognosis in colorectal cancer occurring in cancer-prone patients. 相似文献
87.
Hein J Verberne Petra Dibbets-Schneider Astrid Spijkerboer Marcel Stokkel Berthe L F van Eck-Smit Ellinor Busemann Sokole 《Journal of nuclear cardiology》2006,13(6):801-810
BACKGROUND: A multicenter intercomparison assessment was made of the variation in left ventricular (LV) volumes and ejection fractions (EFs) obtained from gated myocardial perfusion single photon emission computed tomography (SPECT) of the 3-dimensional AGATE (Amsterdam gated) cardiac phantom. METHODS AND RESULTS: The phantom was configured to produce 3 different standard end-systolic volume and end-diastolic volume combinations (50 mL and 120 mL, 90 mL and 160 mL, and 120 mL and 190 mL) with corresponding EF (58%, 44%, and 37%). Quantitative gated myocardial perfusion SPECT was performed with 39 SPECT systems in 35 departments. In the multicenter study, for all 3 filling conditions, a wide range of results was obtained. The EF was overestimated (by 1% to 15%), and both the end-systolic volume and end-diastolic volume were underestimated (by 1 to 65 mL). The extent of overestimation of EF was related to the extent of underestimation of the volumes and was independent of filling condition. The trend in error per center was comparable for all 3 filling conditions. Acquisition time per projection was the only independent predictor of the difference between measured and expected EF (P = .0001). CONCLUSIONS: Care should be taken before extrapolation of published and accepted cutoff values for LV EF and volumes in clinical decision making. Results should be validated in each center and monitored for accuracy and consistency over time. 相似文献
88.
Expression of the BCRP gene (ABCG2/MXR/ABCP) in childhood acute lymphoblastic leukaemia 总被引:8,自引:0,他引:8
The breast cancer resistance protein (BCRP), also known as mitoxantrone resistance protein (MXR) or placenta ABC protein (ABC-P), is the second member of the ABCG subfamily of ABC transport proteins (gene symbol ABCG2). BCRP has been detected in acute myeloid leukaemia and in breast, colon and gastric cancer but there has been no reports regarding BCRP expression in acute lymphoblastic leukaemia (ALL). We report the first results of BCRP expression in childhood ALL. Sixty-seven children (47 initial stage, 20 relapses) with ALL were analysed for BCRP gene expression by TaqMan real-time polymerase chain reaction. The expression of BCRP in mononuclear cells obtained from the bone marrow (BM) and peripheral blood (PB) of healthy donors was also investigated. There was no relationship between BCRP expression and age, sex, initial blast cell count, prednisolone response or BM response on d 15 and 33. Patients with T-lineage ALL showed a lower expression of BCRP (P = 0.044). Kaplan-Meier analysis of the relapse-free interval showed no prognostic significance of BCRP expression when different levels of BCRP expression were used as cut-off points. No significant difference in expression of BCRP mRNA was measured between initial-stage and relapsed-stage ALL or between normal MNC obtained from BM and ALL patients. The results indicate a low expression of BCRP in childhood ALL. Relationships between BCRP and clinical, molecular or in vivo resistance characteristics of the patients were not observed. 相似文献
89.
We studied the effects of long-term (i.e. 4 wk) voluntary exercise on the hypothalamic-pituitary-adrenocortical (HPA) axis in male mice. Voluntary exercise was provided by giving mice access to a running wheel, in which they indeed ran for about 4 km/d. Exercising mice showed similar body weights as control animals but presented less abdominal fat, lighter thymuses, and heavier adrenal glands. Exercise resulted in asymmetric structural changes in the adrenal glands. Whereas control mice had larger left than right adrenals, this condition was abolished in exercising animals, mainly because of enlargement of the right adrenal cortex. Tyrosine hydroxylase mRNA expression in the adrenal medullas of exercising mice was increased. In exercising mice, early-morning baseline plasma ACTH levels were decreased, whereas plasma corticosterone levels at the start of the dark phase were twice as high as those in control animals. To forced swimming and restraint stress, exercising mice responded with higher corticosterone levels than those of the control animals but with similar ACTH levels. However, if exposed to a novel environment, then exercising mice presented decreased ACTH responses. Interestingly, exercising mice showed a decreased corticosterone response to novelty only when the novel environment contained a functioning running wheel. Glucocorticoid receptor levels were unchanged, whereas mineralocorticoid receptor levels were decreased, in hippocampus of exercising animals. Corticotropin-releasing factor mRNA levels in the paraventricular nucleus were lower in exercising mice. Thus, voluntary exercise results in complex, adaptive changes at various levels within the HPA axis as well as in sympathoadrenomedullary and limbic/neocortical afferent control mechanisms. These changes seem to underlie the differential responsiveness of the HPA axis to physical vs. emotional challenges. 相似文献
90.
Wieneke Vlastra MD PhD Astrid C. van Nieuwkerk MD Anne-Sophie G.T. Bronzwaer PhD Adriaan Versteeg BSc Esther E. Bron PhD Wiro J. Niessen MD PhD Henk J.M.M. Mutsaerts MD PhD Björn J.P. van der Ster MSc Charles B.L.M. Majoie MD PhD Geert J. Biessels MD PhD Aart J. Nederveen MD PhD Mat J.A.P. Daemen MD PhD Matthias J.P. van Osch PhD Jan Baan MD PhD Jan J. Piek MD PhD Johannes J. Van Lieshout MD PhD Ronak Delewi MD PhD 《Journal of the American Geriatrics Society》2021,69(2):494-499