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31.
Targeting of heat shock protein 32 (Hsp32)/heme oxygenase-1 (HO-1) in leukemic cells in chronic myeloid leukemia: a novel approach to overcome resistance against imatinib 下载免费PDF全文
Mayerhofer M Gleixner KV Mayerhofer J Hoermann G Jaeger E Aichberger KJ Ott RG Greish K Nakamura H Derdak S Samorapoompichit P Pickl WF Sexl V Esterbauer H Schwarzinger I Sillaber C Maeda H Valent P 《Blood》2008,111(4):2200-2210
Resistance toward imatinib and other BCR/ABL tyrosine kinase inhibitors remains an increasing clinical problem in the treatment of advanced stages of chronic myeloid leukemia (CML). We recently have identified the heat shock protein 32 (Hsp32)/heme oxygenase-1 (HO-1) as a BCR/ABL-dependent survival molecule in CML cells. We here show that silencing Hsp32/HO-1 in CML cells by an siRNA approach results in induction of apoptosis. Moreover, targeting Hsp32/HO-1 by either pegylated zinc protoporphyrine (PEG-ZnPP) or styrene maleic acid-micelle-encapsulated ZnPP (SMA-ZnPP) resulted in growth inhibition of BCR/ABL-transformed cells. The effects of PEG-ZnPP and SMA-ZnPP were demonstrable in Ba/F3 cells carrying various imatinib-resistant mutants of BCR/ABL, including the T315I mutant, which exhibits resistance against all clinically available BCR/ABL tyrosine kinase inhibitors. Growth-inhibitory effects of PEG-ZnPP and SMA-ZnPP also were observed in the CML-derived human cell lines K562 and KU812 as well as in primary leukemic cells obtained from patients with freshly diagnosed CML or imatinib-resistant CML. Finally, Hsp32/HO-1-targeting compounds were found to synergize with either imatinib or nilotinib in producing growth inhibition in imatinib-resistant K562 cells and in Ba/F3 cells harboring the T315I mutant of BCR/ABL. In summary, these data show that HO-1 is a promising novel target in imatinib-resistant CML. 相似文献
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Generation and characterization of highly purified canine Schwann cells from spinal nerve dorsal roots as potential new candidates for transplantation strategies 下载免费PDF全文
Ingo Gerhauser Yimin Wang Regina Carlson Andrea Tipold Wolfgang Baumgärtner Veronika M. Stein 《Journal of tissue engineering and regenerative medicine》2018,12(1):e422-e437
Schwann cells are promising candidates for transplantation strategies in the central nervous system by promoting axonal regeneration. The dog represents a translational model for human spinal cord injury (SCI) for studies with new repair strategies after intervertebral disk herniation (IVDH). To overcome the necessity for an additional surgical procedure, for the first time a protocol for the isolation and purification of canine Schwann cells from spinal nerve biopsies during standard hemilaminectomy in IVDH‐affected paraplegic dogs for potential transplantation has been developed. Purity was assessed by flow cytometry. The results were compared with biopsies from dogs without SCI. Within 26 ± 4 days, 90.2 ± 8.8% p75 neurotrophin receptor (p75NTR)‐positive cells were achieved in IVDH dogs. The total cell count in acute/subacute and chronic IVDH (acute/subacute: 6.82 ± 6.36 × 106; chronic: 2.29 ± 2.00 × 106) differed significantly (p = 0.0120) at the potential time point of transplantation. No differences in culture period and purity were detected between dogs with and without IVDH. Despite the small sample size and the altered environment, the isolation of Schwann cells was successful. Negative influences on isolation and purification due to potential pathological changes at the biopsy site of IVDH‐diseased dogs were ruled out by comparison of Schwann cell pellets from diseased and control dogs. Finally, the functionality of Schwann cells from dogs with IVDH was outlined in co‐culture experiments with canine dorsal root ganglion neurons. In conclusion, nerve root biopsies provide a sufficient number of highly purified and functional Schwann cells within a useful time period for novel therapeutic strategies in dogs with SCI. 相似文献
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Red blood cells treated with the amustaline (S‐303) pathogen reduction system: a transfusion study in cardiac surgery 下载免费PDF全文
Veronika Brixner Arndt‐Holger Kiessling Katharina Madlener Markus M. Müller Johannes Leibacher Sarah Dombos Iuliia Weber Hans‐Ulrich Pfeiffer Christof Geisen Michael Schmidt Reinhard Henschler Anne North Norman Huang Nina Mufti Anna Erickson Christine Ernst Salvador Rico Richard J. Benjamin Laurence M. Corash Erhard Seifried 《Transfusion》2018,58(4):905-916
36.
Mitochondrial DNA multiplex real‐time polymerase chain reaction inhibition assay for quality control of pathogen inactivation by ultraviolet C light in platelet concentrates 下载免费PDF全文
37.
Lukasova Vera Buzgo Matej Vocetkova Karolina Kubíkov Tereza Tonar Zbynk Doupnik Miroslav Blahnova Veronika Litvinec Andrej Sovkova Vera Voltrov Barbora Staffa Andrea Svora Petr Kralickova Milena Amler Evzen Filova Eva Rustichelli Franco Rampichova Michala 《RSC advances》2018,8(39):21889
Bone regeneration is a long-term process requiring proper scaffolding and drug delivery systems. The current study delivers a three-dimensional (3D) scaffold prepared by blend centrifugal spinning loaded with the osteogenic supplements (OS) β-glycerol phosphate, ascorbate-2-phosphate and dexamethasone. The OS were successfully encapsulated into a fibrous scaffold and showed sustained release for 30 days. Furthermore, biological testing showed the osteoinductive properties of the scaffolds on a model of human mesenchymal stem cells and stimulatory effect on a model of osteoblasts. The osteoinductive properties were further proved in vivo in critical size defects of rabbits. The amount of bone trabecules was bigger compared to control fibers without OS. The results indicate that due to its long-term drug releasing properties, single step fabrication process and 3D structure, the system shows ideal properties for use as a cell-free bone implant in tissue-engineering.Bone regeneration is a long-term process requiring proper scaffolding and drug delivery systems. 相似文献
38.
The lung vasculature bed has a unique fibrinolytic potential, which has not yet been completely elucidated. We investigated the effect of blood passage through the pulmonary circulation on the values of fibrinolytic parameters in plasma. Forty-seven patients (16 women, 31 men, mean age 54 years, range 21–67 years) who had undergone elective cardiac catheterization were included in the study. The blood samples were taken simultaneously from the right atrium and the left ventricle. The following fibrinolytic parameters were measured: tissue-type plasminogen (t-PA) antigen and activity, plasminogen activator inhibitor-1 (PAI-1) antigen and activity, and euglobulin clot lysis time (ECLT). No difference was found between the samples obtained from the right atrium and the left ventricle with respect to t-PA antigen: 8.1 (6.7–11.3) vs 8.4 (5.9–11.0)ng/ml; t-PA activity: 92 (5–680) vs 62 (32–696)IU/ml; PAI-1 antigen: 8.4 (5.5–14.3) vs 8.7 (6.2–13.1)ng/ml; and ECLT: 5.5 (4.1–9.1) vs 5.6 (4.1–8.5) 1000/min. In contrast, PAI activity decreased significantly: 7.9 (5.8–10.3) vs 7.4 (6.0–10.4)IU/ml, P 0.01. Patients with and without pulmonary hypertension did not differ in any of measured parameters, either in the right atrium or in the left ventricle. These results show that under basal conditions fibrinolytic activity which is not attributed to t-PA is elevated in lung vasculature. Further, basal fibrinolytic activity in the lungs is not influenced by pulmonary hypertension. 相似文献
39.
Facial clefts are among the most common congenital defects. Ultrasound (US) imaging of secondary fetal palate, especially the detection of isolated defects, remains challenging. Currently described two‐dimensional (2D) and three‐dimensional methods are technically demanding and impractical for application during routine fetal anatomy evaluation. As an adjunct method, magnetic resonance imaging can provide additional information but has its limitations. We present a novel 2D US approach using axial and sagittal planes to evaluate the fetal palate and demonstrate the main differences between an intact palate, isolated cleft palate, and a cleft lip with cleft palate. 相似文献