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Radhakrishnan Sabarinathan Hakim Tafer Stefan E. Seemann Ivo L. Hofacker Peter F. Stadler Jan Gorodkin 《Human mutation》2013,34(4):546-556
Structural characteristics are essential for the functioning of many noncoding RNAs and cis‐regulatory elements of mRNAs. SNPs may disrupt these structures, interfere with their molecular function, and hence cause a phenotypic effect. RNA folding algorithms can provide detailed insights into structural effects of SNPs. The global measures employed so far suffer from limited accuracy of folding programs on large RNAs and are computationally too demanding for genome‐wide applications. Here, we present a strategy that focuses on the local regions of maximal structural change between mutant and wild‐type. These local regions are approximated in a “screening mode” that is intended for genome‐wide applications. Furthermore, localized regions are identified as those with maximal discrepancy. The mutation effects are quantified in terms of empirical P values. To this end, the RNAsnp software uses extensive precomputed tables of the distribution of SNP effects as function of length and GC content. RNAsnp thus achieves both a noise reduction and speed‐up of several orders of magnitude over shuffling‐based approaches. On a data set comprising 501 SNPs associated with human‐inherited diseases, we predict 54 to have significant local structural effect in the untranslated region of mRNAs. RNAsnp is available at http://rth.dk/resources/rnasnp . 相似文献
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Fernando Augusto Vasilceac Rita de Cássia Marqueti Ivo Vieira de Sousa Neto Dahan da Cunha Nascimento Mariana Carvalho de Souza João Luiz Quaglioti Durigan Stela Márcia Mattiello 《Revista brasileira de fisioterapia (S?o Carlos (S?o Paulo, Brazil))》2021,25(2):147-155
BackgroundOsteoarthritis (OA) is a degenerative disease that induces peri-articular tissue degradation. OA induces an imbalance between synthesis and degradation of the extracellular matrix components in favor of catabolic events, promoting pathological remodeling and involving degradative enzymes, such as matrix metalloproteinases (MMPs).ObjectiveThis study aimed to investigate the effects of 8-weeks resistance training (RT) on MMP-2 activity in the quadriceps tendon and patellar tendon in an OA model.MethodsTwenty-four Wistar rats were randomly divided into six groups: Control, Exercise, Sham, Sham with Exercise, OA, and OA with Exercise (OAE). The OA model was performed by anterior cruciate ligament transection surgery on the left knee. The 8-week RT consisted of climbing a 1.1-m vertical ladder three times per week with progressive weights secured to the animals’ tails. MMP-2 activity was analyzed by zymography.ResultsThe OAE group displayed lower pro, intermediate, and active MMP-2 activity in the quadriceps tendon compared with the OA group (p < 0.05). For the patellar tendon, there was no significant difference between the OAE group compared with the other groups (p > 0.05) for pro, intermediate, and active MMP-2 activity. Moreover, MMP-2 activity differed between tissues, the OA and OAE groups presented lower pro, intermediate, and active MMP-2 activity in the quadriceps tendon compared to the patellar tendon.ConclusionRT induced down-regulated MMP-2 activity in the quadriceps tendon. RT is a potential therapeutic approach to minimize the deleterious effects of extracellular matrix degeneration. 相似文献
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Associations of 25‐Hydroxyvitamin D and 1,25‐Dihydroxyvitamin D With Bone Mineral Density,Bone Mineral Density Change,and Incident Nonvertebral Fracture 下载免费PDF全文
Christine M Swanson Priya Srikanth Christine G Lee Steven R Cummings Ivo Jans Jane A Cauley Roger Bouillon Dirk Vanderschueren Eric S Orwoll Carrie M Nielson for the Osteoporotic Fractures in Men MrOS Study Research Group 《Journal of bone and mineral research》2015,30(8):1403-1413
Relationships between 1,25‐dihydroxyvitamin D (1,25(OH)2D) and skeletal outcomes are uncertain. We examined the associations of 1,25(OH)2D with bone mineral density (BMD), BMD change, and incident non‐vertebral fractures in a cohort of older men and compared them with those of 25‐hydroxyvitamin D (25OHD). The study population included 1000 men (aged 74.6 ± 6.2 years) in the Osteoporotic Fractures in Men (MrOS) study, of which 537 men had longitudinal dual‐energy X‐ray absorptiometry (DXA) data (4.5 years of follow‐up). A case‐cohort design and Cox proportional hazards models were used to test the association between vitamin D metabolite levels and incident nonvertebral and hip fractures. Linear regression models were used to estimate the association between vitamin D measures and baseline BMD and BMD change. Interactions between 25OHD and 1,25(OH)2D were tested for each outcome. Over an average follow‐up of 5.1 years, 432 men experienced incident nonvertebral fractures, including 81 hip fractures. Higher 25OHD was associated with higher baseline BMD, slower BMD loss, and lower hip fracture risk. Conversely, men with higher 1,25(OH)2D had lower baseline BMD. 1,25(OH)2D was not associated with BMD loss or nonvertebral fracture. Compared with higher levels of calcitriol, the risk of hip fracture was higher in men with the lowest 1,25(OH)2D levels (8.70 to 51.60 pg/mL) after adjustment for baseline hip BMD (hazard ratio [HR] = 1.99, 95% confidence interval [CI] 1.19–3.33). Adjustment of 1,25(OH)2D data for 25OHD (and vice versa) had little effect on the associations observed but did attenuate the hip fracture association of both vitamin D metabolites. In older men, higher 1,25(OH)2D was associated with lower baseline BMD but was not related to the rate of bone loss or nonvertebral fracture risk. However, with BMD adjustment, a protective association for hip fracture was found with higher 1,25(OH)2D. The associations of 25OHD with skeletal outcomes were generally stronger than those for 1,25(OH)2D. These results do not support the hypothesis that measures of 1,25(OH)2D improve the ability to predict adverse skeletal outcomes when 25OHD measures are available. © 2015 American Society for Bone and Mineral Research. 相似文献
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Nicola M. Martucci Ilaria Rea Immacolata Ruggiero Monica Terracciano Luca De Stefano Nunzia Migliaccio Camillo Palmieri Giuseppe Scala Paolo Arcari Ivo Rendina Annalisa Lamberti 《Biomedical optics express》2015,6(4):1353-1362
In this paper, a new strategy for highly selective and sensitive direct detection of lymphoma cells by exploiting the interaction between a peptide and its B-cell receptor, has been evaluated. In particular, an idiotype peptide, able to specifically bind the B-cell receptor of A20 cells in mice engrafted with A20 lymphoma, has been used as molecular probe. The new detection technique has been demonstrated on a planar crystalline silicon chip. Coverage of 85% of silicon surface and detection efficiency of 8.5 × 10−3 cells/μm2 were obtained. The recognition strategy promises to extend its application in studying the interaction between ligands and their cell-surface receptors.OCIS codes: (000.1430) Biology and medicine, (280.1415) Biological sensing and sensors 相似文献
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Mundhenke C Weigel MT Sturner KH Roesel F Meinhold-Heerlein I Bauerschlag DO Schem C Hilpert F Jonat W Maass N 《Journal of cancer research and clinical oncology》2008,134(12):1397-1405
Purpose Imatinib is a small molecule inhibiting the tyrosine kinases bcr-abl, c-kit, PDGFR-α and PDGFR-β. Investigations were performed
to screen ovarian cancer cell lines and tumor samples for target receptor expression. Effects of Imatinib on cell proliferation
and apoptosis induction were measured with and without additional cytotoxic agents.
Methods Expression patterns of abl, c-kit, PDGFR-α and PDGFR-β (Imatinib targets) were studied in 5 cell lines and 111 tissue arrays
by PCR and immunohistochemistry. Proliferation assays were performed with single agent Imatinib or combined with Paclitaxel
and Carboplatin. Apoptosis was measured by DNA fragmentation.
Results All cell lines expressed abl and PDGFR-β. C-kit was only expressed in 2/5 cell lines and PDGFR-α in 4/5. Imatinib reduced
cell growth and lead to pro-apoptotic changes. Combination of Carboplatin, Paclitaxel and Imatinib showed synergistic activity.
Conclusions Our results suggest that Imatinib may be useful for the specific treatment of ovarian cancer as an add-on to conventional
chemotherapy.
C. Mundhenke and M. T. Weigel contributed equally to this work. 相似文献