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91.
Fluorescent in vivo tracking of hematopoietic cells. Part I. Technical considerations 总被引:3,自引:1,他引:3
We report a new technology for in vivo tracking of hematopoietic cells, using fluorescent lipophilic probes. Because the probe is irreversibly bound in the lipids of the cell membrane; substantial numbers of dye molecules can be incorporated per cell and thus substantial signal to noise can be achieved. Although this technology can be used for all hematopoietic cells, these first findings are reported on red blood cells (RBCs) owing to the importance of the membrane to RBC function and integrity. We demonstrated that labeling 10% of the RBCs of a rabbit and reinjecting them into the animal makes possible the tracking of these cells at various times after injection. Furthermore, the labeling appears not to affect in vivo cell lifetime or cellular volume changes in response to hypotonic shock. The single cell fluorescence intensity of the labeled RBCs remains relatively constant for 60 days, and an immune response appears not to be generated against labeled cells. That labeled RBCs have lifetime kinetics in vivo, as shown in other studies, indicates that the membranes are functioning normally and are unaltered by the labeling technology. The technology we present is also applicable to white blood cells, bone marrow, and platelets. 相似文献
92.
Comparison of HIV Type 1 ADA gp120 monomers versus gp140 trimers as immunogens for the induction of neutralizing antibodies 总被引:10,自引:0,他引:10
Kim M Qiao ZS Montefiori DC Haynes BF Reinherz EL Liao HX 《AIDS research and human retroviruses》2005,21(1):58-67
Designing an immunogen for effective neutralizing antibody induction against diverse primary isolates of human immunodeficiency virus type 1 (HIV-1) is a high priority for HIV-1 vaccine development. Soluble gp120 envelope (Env) glycoprotein subunit vaccines elicit high titers of antibodies that neutralize T cell line-adapted (TCLA) strains but the antibodies possess poor neutralizing activity against many primary isolates. Previously, we generated soluble trimeric recombinant gp140 from the HIV-1 primary isolate ADA. Here we compared monomeric ADAgp120 and trimeric ADAgp140 as immunogens for neutralizing antibody responses in guinea pigs. Both immunogens generated a neutralizing antibody response that was detectable against the vaccine strain and several heterologous strains. The magnitude of this response was significantly greater in ADAgp140-immunized animals when measured against the TCLA strain, MN, and the R5 primary isolate, Bal. Two additional isolates (SS1196 and Bx08) were neutralized equally by sera from both groups of animals whereas other isolates were neutralized weakly or not at all. Despite equal titers of V3 loop specific binding antibodies in sera from both groups of animals, neutralization of ADA by sera from gp140-immunized animals was insensitive to the presence of ADA-V3 peptide, whereas addition of this peptide to sera from gp120- immunized animals blocked all detectable neutralizing activity against ADA. These results support the idea that trimeric gp140 is an improved immunogen compared to monomeric gp120 but that additional improvements are required to afford broad protection against a spectrum of heterologous primary HIV-1 isolates. This ADAgp140 immunogen may be considered a starting point from which to engineer additional improvements for cross-reactive neutralizing antibody induction. 相似文献
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Paul Declerck Georgios Bakalos Elias Zintzaras Bettina Barton Thomas Schreitmüller 《Clinical therapeutics》2018,40(5):798-809.e2
Purpose
With the introduction of biosimilars of anticancer monoclonal antibodies (mAbs) in oncology, physicians are potentially confronted with the question whether it is clinically adequate to switch patients who are clinically stable on treatment with the reference product to a newly available biosimilar (or vice versa/from 1 biosimilar to another). For a proper impact assessment of switching, robust, product-specific, and clinically relevant evidence should be required, ideally including data from appropriately designed switching studies. In this article, we assess the current body of switching data available for approved or proposed biosimilars of anticancer mAbs.Methods
PubMed was systematically searched and ClinicalTrials.gov and abstract databases of selected congresses were hand-searched to identify all switching studies including biosimilars of anticancer mAbs.Findings
We identified 8 switching studies with biosimilars of rituximab (CT-P10, GP2013, PF-05280586, and BCD-020) and trastuzumab (ABP 980). Two were performed in oncology indications and the other 6 in rheumatoid arthritis (RA). Key elements of a well-designed switching study, such as randomization and blinding, were contained in several of the studies, but significant limitations were also present. The most frequent limitations were low statistical power because of small patient numbers, lack of an appropriate control arm, short follow-up, chosen outcome measures, and (for studies performed in RA) the concern whether switching data can be extrapolated to oncology indications. Accordingly, the data from these studies need to be interpreted with caution. Of note, all identified studies included a single switch only, whereas multiple switches may occur in the real-world setting. The scientific need to evaluate the impact of repeated switching has been recognized by the US Food and Drug Administration, who incorporated such a requirement in its draft guidance on interchangeability.Implications
From the scarce data available, the consequences of switching between reference product mAbs and their biosimilar(s) in the oncology setting are as yet unknown. Additional clinical evidence from well-designed switching studies is needed to guide switching decisions. 相似文献95.
96.
Singh Jasvinder A. Richards John S. Chang Elizabeth Toupin-April Karine Barton Jennifer L. 《Clinical rheumatology》2021,40(2):693-700
Clinical Rheumatology - To assess rheumatologists’ views and practices related to shared decision-making (SDM) in gout treatment. We performed a cross-sectional electronic survey of... 相似文献
97.
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99.
R S Thrall R W Barton D A D'Amato S B Sulavik 《The American review of respiratory disease》1982,126(3):488-492
The purpose of this study was to analyze the cellular components of bronchoalveolar lavage fluid throughout the development of bleomycin-induced pulmonary fibrosis in the rat. Animals were killed and lavaged at various times after the administration of a single intratracheal injection of bleomycin. The results demonstrate that a significant influx of inflammatory cells appear in the lavage fluid as early as Day 1 after bleomycin treatment. Polymorphonuclear leukocytes are the first cells to appear and significant concentrations persist for as long as 1 month after bleomycin treatment. There is a very transient yet significant influx of eosinophils on Day 7 after bleomycin treatment. Lymphocytes are present from 3 to 14 days after bleomycin treatment; greater than 97% are T-cells and less than 3% are B-cells. There is a 1:1 ratio of W3/25+ cells (helper cell activity) to OX8+ cells (suppressor cell activity) comprising the lymphocyte population. The blood and lymphoid tissue of these animals contain a normal 2:1 ratio of these subsets. The data demonstrate that specific T-cell populations are present in the air spaces of the lung in response to bleomycin-induced pulmonary fibrosis in this model. 相似文献
100.