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991.
The Viral Replication Complex Is Associated with the Virulence of Newcastle Disease Virus 总被引:1,自引:0,他引:1
J. C. F. M. Dortmans P. J. M. Rottier G. Koch B. P. H. Peeters 《Journal of virology》2010,84(19):10113-10120
992.
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994.
Marco Pompei Maria Emilia Di Francesco Silvia Pesci Uwe Koch Sue Ellen Vignetti Maria Veneziano Paola Pace Vincenzo Summa 《Bioorganic & medicinal chemistry letters》2010,20(1):168-174
Hepatitis C represents a serious worldwide health-care problem. Recently, we have disclosed a novel class of P2–P4 macrocyclic inhibitors of NS3/4A protease containing a carbamate functionality as capping group at the P3 N-terminus. Herein we report our work aimed at further depeptidizing the P3 region by replacement of the urethane function with a succinamide motif. This peptidomimetic approach has led to the discovery of novel P2–P4 macrocyclic inhibitors of HCV NS3/4A protease with sub-nanomolar enzyme affinities. In addition to being potent inhibitors of HCV subgenomic replication, optimized analogues within this series have also presented attractive PK properties and showed promising liver levels in rat following oral administration. 相似文献
995.
Koch M Chitayat S Dattilo BM Schiefner A Diez J Chazin WJ Fritz G 《Structure (London, England : 1993)》2010,18(10):1342-1352
The receptor for advanced glycation end products (RAGE) is a pattern recognition receptor involved in?inflammatory processes and is associated with diabetic complications, tumor outgrowth, and neurodegenerative disorders. RAGE induces cellular signaling events upon binding of a variety of ligands, such as glycated proteins, amyloid-β, HMGB1, and S100 proteins. The X-ray crystal structure of the VC1 ligand-binding region of the human RAGE ectodomain was determined at 1.85?? resolution. The VC1 ligand-binding surface was mapped onto the structure from titrations with S100B monitored by heteronuclear NMR spectroscopy. These NMR chemical shift perturbations were used as input for restrained docking calculations to generate a model for the VC1-S100B complex. Together, the arrangement of VC1 molecules in the crystal and complementary biochemical studies suggest a role for self-association in RAGE function. Our results enhance understanding of the functional outcomes of S100 protein binding to RAGE and provide insight into mechanistic models for how the receptor is activated. 相似文献
996.
Jessica Hoppst?dter Britta Diesel Robert Zarbock Tanja Breinig Dominik Monz Marcus Koch Andreas Meyerhans Ludwig Gortner Claus-Michael Lehr Hanno Huwer Alexandra K Kiemer 《Respiratory research》2010,11(1):124
Background
Investigations on pulmonary macrophages (MΦ) mostly focus on alveolar MΦ (AM) as a well-defined cell population. Characteristics of MΦ in the interstitium, referred to as lung interstitial MΦ (IM), are rather ill-defined. In this study we therefore aimed to elucidate differences between AM and IM obtained from human lung tissue.Methods
Human AM and IM were isolated from human non-tumor lung tissue from patients undergoing lung resection. Cell morphology was visualized using either light, electron or confocal microscopy. Phagocytic activity was analyzed by flow cytometry as well as confocal microscopy. Surface marker expression was measured by flow cytometry. Toll-like receptor (TLR) expression patterns as well as cytokine expression upon TLR4 or TLR9 stimulation were assessed by real time RT-PCR and cytokine protein production was measured using a fluorescent bead-based immunoassay.Results
IM were found to be smaller and morphologically more heterogeneous than AM, whereas phagocytic activity was similar in both cell types. HLA-DR expression was markedly higher in IM compared to AM. Although analysis of TLR expression profiles revealed no differences between the two cell populations, AM and IM clearly varied in cell reaction upon activation. Both MΦ populations were markedly activated by LPS as well as DNA isolated from attenuated mycobacterial strains (M. bovis H37Ra and BCG). Whereas AM expressed higher amounts of inflammatory cytokines upon activation, IM were more efficient in producing immunoregulatory cytokines, such as IL10, IL1ra, and IL6.Conclusion
AM appear to be more effective as a non-specific first line of defence against inhaled pathogens, whereas IM show a more pronounced regulatory function. These dissimilarities should be taken into consideration in future studies on the role of human lung MΦ in the inflammatory response. 相似文献997.
998.
Jeffrey H Ruth Christy C Park M Asif Amin Charles Lesch Hubert Marotte Shiva Shahrara Alisa E Koch 《Arthritis research & therapy》2010,12(3):R118
Introduction
The function of interleukin-18 (IL-18) was investigated in pertinent animal models of rodent rheumatoid arthritis (RA) to determine its proinflammatory and monocyte recruitment properties. 相似文献999.
Noncanonical tandem SH2 enables interaction of elongation factor Spt6 with RNA polymerase II 总被引:1,自引:0,他引:1
Diebold ML Loeliger E Koch M Winston F Cavarelli J Romier C 《The Journal of biological chemistry》2010,285(49):38389-38398
1000.
Marc J. Berna Oliver Seiz Jan Friso Nast Daniel Benten Michael Bl?ker Johannes Koch Ansgar W. Lohse Andrea Pace 《The Journal of biological chemistry》2010,285(50):38905-38914
The gastrointestinal hormone cholecystokinin (CCK) can induce acute pancreatitis in rodents through its action on acinar cells. Treatment with CCK, in combination with other agents, represents the most commonly used model to induce experimental chronic pancreatitis. Pancreatic stellate cells (PSC) are responsible for pancreatic fibrosis and therefore play a predominant role in the genesis of chronic pancreatitis. However, it is not known whether PSC express CCK receptors. Using real time PCR techniques, we demonstrate that CCK1 and CCK2 receptors are expressed on rat PSC. Interestingly both CCK and gastrin significantly induced type I collagen synthesis. Moreover, both inhibit proliferation. These effects are comparable with TGF-β-stimulated PSC. Furthermore, the natural agonists CCK and gastrin induce activation of pro-fibrogenic pathways Akt, ERK, and Src. Using specific CCK1 and CCK2 receptor (CCK2R) inhibitors, we found that Akt activation is mainly mediated by CCK2R. Akt activation by CCK and gastrin could be inhibited by the PI3K inhibitor wortmannin. Activation of ERK and the downstream target Elk-1 could be inhibited by the MEK inhibitor U0126. These data suggest that CCK and gastrin have direct activating effects on PSC, are able to induce collagen synthesis in these cells, and therefore appear to be important regulators of pancreatic fibrogenesis. Furthermore, similar to TGF-β, both CCK and gastrin inhibit proliferation in PSC. 相似文献