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81.
82.
对批量伤病员送至医院进入排队系统,实施分级救治,是降低伤死、伤残以及使伤员得到及时治疗的重要措施。本文运用离散事件系统建模的方法、仿真策略和排队系统的仿真方法,建立了伤病员在医院救治的排队论模型,并以武汉汉口遭袭进行仿真和结果分析。 相似文献
83.
药代动力学药效动力学结合模型研究进展 总被引:2,自引:3,他引:2
药代动力学和药效动力学共同构成了现代药理学研究的基础。PK/PD模型是将两者相结合,以说明给予某一剂量后所引起的药理作用的时间过程。研究PK/PD关系不但有助于正确指导临床用药,还可以用于探讨药物作用机制、新药评估以及新制剂的开发等。本文就近些年来PK/PD模型在药理学和毒理学,临床应用以及新药开发等方面的研究进展作一简要的综述。 相似文献
84.
Abstract: Nuclear magnetic resonance (NMR) spectra of a model peptide (BL‐DIS6), in the presence of anticonvulsant diphenyl drug, phenytoin (DPH), were measured to obtain the interactions between the selected drug and the model peptide. BL‐DIS6's sequence corresponds to the S6 segment in domain I of rat brain type IIA Na+‐channel. NMR studies have demonstrated that the magnitude of the chemical shifts of amide‐ and α‐protons can be used as a measurement of the complex stability and binding site of the peptide. Our NMR results propose a 310‐helical structure for BL‐DIS6, and suggest a binding cavity for DPH that involves the hydrophobic particles of residues Ans‐7, Leu‐8, Val‐11, and Val‐12. Furthermore, molecular modeling was performed to provide a possible complex conformation that the phenyl portion of DPH is accommodated in the proximity of the C‐terminal residues Ala‐11 and Val‐12, and simultaneously the heterocyclic amine ring of DPH is perching at the residue Asn‐7 periphery and stabilizing the phenyl portion deep insertion into the peptide. 相似文献
85.
Sergio E. Baranzini 《Autoimmunity》2013,46(8):651-662
Systems medicine is an emerging concept that acknowledges the complexity of a multitude of non-linear interactions among molecular and physiological variables. Under this new paradigm, rather than a collection of symptoms, diseases are seen as the product of deviations from a robust steady state compatible with life. This concept requires the incorporation of mathematics and physics to the more classical arsenal of physiology and molecular biology with which physicians are trained today. This review explores the diverse types of information that can be accumulated towards the understanding of multiple sclerosis (MS), a complex autoimmune disease that targets the central nervous system (CNS). The challenge of data integration and modeling of dynamical systems is discussed in the context of disease susceptibility and response to treatment. A theoretical framework that supports the use of combination therapy is also presented. 相似文献
86.
Gentian violet (GV) is a well-known triarylmethane dye that is used in aquacultural, industrial and medicinal fields. But concerns in growing number have been paid to its potential health problems to human beings and its hazardous effects to environment. Herein, the toxic interaction of GV with bovine hemoglobin (BHb) was investigated by a series of spectroscopic methods and molecular modeling method. The fluorescence emission profile exhibited a remarkable quenching upon addition of GV to the buffered aqueous solution of BHb and the analysis of results revealed the dominant role of static quenching mechanism in GV–BHb interaction. The negative ΔH and positive ΔS values demonstrated that the electrostatic interactions mainly stabilized this toxicantprotein complex. Synchronous fluorescence, UV–Vis absorption and CD spectroscopic studies proved that the conformational change of BHb was induced by GV’s combination. Molecular modeling studies exhibited the binding mode of GV–BHb complex and the detailed information of related driving forces. During the 1H nuclear magnetic resonance spectra (1H NMR) study, the chemical shift perturbation and spin–lattice relaxation times of different protons were further used to investigate the interaction of GV with BHb and the results indicated that GV bound orientationally to BHb. 相似文献
87.
DNA-dependent protein kinase (DNA-PK) is a key enzyme in non-homologous DNA end joining (NHEJ) repair pathway. The targeted inhibition of such enzyme would furnish a valuable option for cancer treatment. In this study we report the development of validation of enzyme homology model, and the subsequent use of this model to perform docking-based virtual screening against a database of FDA-approved drugs. The nominated highest ranking hits (Praziquantel and Dutasteride) were subjected to biological investigation. Additionally, molecular dynamic study was carried-out for binding mode exploration. Results of the biological evaluation revealed that both compounds inhibit the DNA-PK enzymatic activity at relatively high concentration levels with an IC50 of 17.3 μM for praziquantel and >20 μM for dutasteride. Furthermore, both agents enhanced the anti-proliferative effects of doxorubicin and cisplatin on breast cancer (MCF7) and lung cancer (A549) cell lines. This result indicates that these two hits are good candidate as DNA-PK inhibitors and worth further structural modifications to enhance their enzyme inhibitory effects. 相似文献
88.
Immuno-pharmacodynamics for evaluating mechanism of action and developing immunotherapy combinations
《Seminars in oncology》2016,43(4):501-513
Immunotherapy has become a major modality of cancer treatment, with multiple new classes of immunotherapeutics recently entering the clinic and obtaining market approval from regulatory agencies. While the promise of these therapies is great, so is the number of possible combinations not only with each other but also with small molecule therapeutics. Furthermore, the observation of unusual dose-response relationships suggests a critical dependency of drug effectiveness on the dosage regimen (dose and schedule). Clinical pharmacodynamic (PD) biomarkers will be useful endpoints for confirming drug mechanism of action, evaluating combination therapies for synergy or antagonism, and identifying optimal dosage regimens. In contrast to conventional PD in which drug action occurs entirely within a single target cell (ie, is self-contained within the malignant cell), immunotherapy involves a complex mechanism of action with sequential steps that propagate through multiple cell types, both normal and malignant. Its intercellular pharmacology begins with molecular target engagement either on an immune effector cell or a malignant cell, followed by stimulatory biochemical and biological signals in immune effector cells, and then finally ends with activation of cell death mechanisms in malignant cells lying within a certain distance from the activated effector cells (immune cell–tumor cell proximity). Evaluating such “trans-cellular pharmacology,” in which different steps of drug action are distributed across multiple cell types, requires novel microscopy and image analysis tools capable of quantifying PD-biomarker responses, mapping the responses onto the cellular geography of the tumor using phenotypic biomarkers to identify specific cell types, and finally analyzing the spatial relationships between biomarkers in the context of each cell’s biological role. We have termed this form of nearest neighbor image analysis of drug action “proximity PD microscopy,” to indicate the importance of the location of the PD-biomarker response within the cellular landscape of a tumor specimen. We discuss herein the major modes of immunotherapy, and lay out a blueprint for using PD assessment to optimize dosage regimens of single agents and guide development of combination immunotherapy regimens, using PD1/PD-L1 immune checkpoint inhibition as a case study. 相似文献
89.
《Expert review of anti-infective therapy》2013,11(3):361-373
Pharmacokinetic/pharmacodynamic modeling has become an extremely important tool in evaluating and optimizing anti-infective therapy. By systematically linking the pharmacokinetic and pharmacodynamic properties of the anti-infective agent, it is possible to make educated decisions about the correct drug to be used, correct dosing regimen and to estimate the probability of success with the selected dose regimen. This article gives an overview of the current pharmacokinetic/pharmacodynamic approaches for anti-infective agents and discusses their use in optimizing drug therapy. 相似文献
90.
《Journal of psychosocial oncology》2013,31(4):59-68
Although the effects of treatment for childhood cancer on subsequent reproductive outcomes are unknown, they are often implicated as contributing to that outcome in a detrimental manner. In this study, 263 adult survivors of childhood cancer were compared with 369 adult sibling controls regarding their decisions to marry and have children. The survivors were more likely to report not marrying for health reasons. Although the long-term surivivors did not have significantly more documented or suspected infertility problems, they were less likely than controls to have been pregnant or involved with a pregnancy and were more likely to have been advised by a physician to avoid a pregnancy. However, when the frequency of birth defects among 253 offspring of the survivors was compared with the frequency of defents among 595 offspring of controls, the outcome of pregnancy among survivors and controls proved to equally favorable. 相似文献