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891.
Activation of stress signalling pathways enhances tolerance of fungi to chemical fungicides and antifungal proteins 总被引:1,自引:0,他引:1
Brigitte M. E. Hayes Marilyn A. Anderson Ana Traven Nicole L. van der Weerden Mark R. Bleackley 《Cellular and molecular life sciences : CMLS》2014,71(14):2651-2666
Fungal disease is an increasing problem in both agriculture and human health. Treatment of human fungal disease involves the use of chemical fungicides, which generally target the integrity of the fungal plasma membrane or cell wall. Chemical fungicides used for the treatment of plant disease, have more diverse mechanisms of action including inhibition of sterol biosynthesis, microtubule assembly and the mitochondrial respiratory chain. However, these treatments have limitations, including toxicity and the emergence of resistance. This has led to increased interest in the use of antimicrobial peptides for the treatment of fungal disease in both plants and humans. Antimicrobial peptides are a diverse group of molecules with differing mechanisms of action, many of which remain poorly understood. Furthermore, it is becoming increasingly apparent that stress response pathways are involved in the tolerance of fungi to both chemical fungicides and antimicrobial peptides. These signalling pathways such as the cell wall integrity and high-osmolarity glycerol pathway are triggered by stimuli, such as cell wall instability, changes in osmolarity and production of reactive oxygen species. Here we review stress signalling induced by treatment of fungi with chemical fungicides and antifungal peptides. Study of these pathways gives insight into how these molecules exert their antifungal effect and also into the mechanisms used by fungi to tolerate sub-lethal treatment by these molecules. Inactivation of stress response pathways represents a potential method of increasing the efficacy of antifungal molecules. 相似文献
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893.
Giorgio Cozza Cristina Girardi Alessandro Ranchio Graziano Lolli Stefania Sarno Andrzej Orzeszko Zygmunt Kazimierczuk Roberto Battistutta Maria Ruzzene Lorenzo A. Pinna 《Cellular and molecular life sciences : CMLS》2014,71(16):3173-3185
It has been proposed that dual inhibitors of protein kinases CK2 and PIM-1 are tools particularly valuable to induce apoptosis of cancer cells, a property, however, implying cell permeability, which is lacking in the case of selective CK2/PIM-1 inhibitors developed so far. To fill this gap, we have derivatized the scaffold of the promiscuous CK2 inhibitor TBI with a deoxyribose moiety, generating TDB, a selective, cell-permeable inhibitor of CK2 and PIM-1. Here, we shed light on the structural features underlying the potency and narrow selectivity of TDB by exploiting a number of TDB analogs and by solving the 3D structure of the TDB/CK2 complex at 1.25?Å resolution, one of the highest reported so far for this kinase. We also show that the cytotoxic efficacy of TDB is almost entirely due to apoptosis, is accompanied by parallel inhibition of cellular CK2 and PIM-1, and is superior to both those observed combining individual inhibitors of CK2 and PIM-1 and by treating cells with the CK2 inhibitor CX4945. These data, in conjunction with the observations that cancer cells are more susceptible than non-cancer cells to TDB and that such a sensitivity is maintained in a multi-drug resistance background, highlight the pharmacological potential of this compound. 相似文献
894.
Sara B. Seidelmann Janet K. Lighthouse Daniel M. Greif 《Cellular and molecular life sciences : CMLS》2014,71(11):1977-1999
Arteries consist of an inner single layer of endothelial cells surrounded by layers of smooth muscle and an outer adventitia. The majority of vascular developmental studies focus on the construction of endothelial networks through the process of angiogenesis. Although many devastating vascular diseases involve abnormalities in components of the smooth muscle and adventitia (i.e., the vascular wall), the morphogenesis of these layers has received relatively less attention. Here, we briefly review key elements underlying endothelial layer formation and then focus on vascular wall development, specifically on smooth muscle cell origins and differentiation, patterning of the vascular wall, and the role of extracellular matrix and adventitial progenitor cells. Finally, we discuss select human diseases characterized by marked vascular wall abnormalities. We propose that continuing to apply approaches from developmental biology to the study of vascular disease will stimulate important advancements in elucidating disease mechanism and devising novel therapeutic strategies. 相似文献
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897.
Snake venom contains mixture of bioactive proteins and polypeptides. Most of these proteins and polypeptides exist as monomers,
but some of them form complexes in the venom. These complexes exhibit much higher levels of pharmacological activity compared
to individual components and play an important role in pathophysiological effects during envenomation. They are formed through
covalent and/or non-covalent interactions. The subunits of the complexes are either identical (homodimers) or dissimilar (heterodimers;
in some cases subunits belong to different families of proteins). The formation of complexes, at times, eliminates the non-specific
binding and enhances the binding to the target molecule. On several occasions, it also leads to recognition of new targets
as protein-protein interaction in complexes exposes the critical amino acid residues buried in the monomers. Here, we describe
the structure and function of various protein complexes of snake venoms and their role in snake venom toxicity. 相似文献
898.
899.
Celiac disease IgA modulates vascular permeability in vitro through the activity of transglutaminase 2 and RhoA 总被引:1,自引:1,他引:0
Essi Myrsky Sergio Caja Zsofi Simon-Vecsei Ilma R. Korponay-Szabo Cristina Nadalutti Russell Collighan Alexandre Mongeot Martin Griffin Markku Mäki Katri Kaukinen Katri Lindfors 《Cellular and molecular life sciences : CMLS》2009,66(20):3375-3385
Celiac disease is characterized by the presence of specific autoantibodies targeted against transglutaminase 2 (TG2) in untreated patients’ serum and at their production site in the small-bowel mucosa below the basement membrane and around the blood vessels. As these autoantibodies have biological activity in vitro, such as inhibition of angiogenesis, we studied if they might also modulate the endothelial barrier function. Our results show that celiac disease patient autoantibodies increase endothelial permeability for macromolecules, and enhance the binding of lymphocytes to the endothelium and their transendothelial migration when compared to control antibodies in an endothelial cell-based in vitro model. We also demonstrate that these effects are mediated by increased activities of TG2 and RhoA. Since the small bowel mucosal endothelium serves as a “gatekeeper” in inflammatory processes, the disease-specific autoantibodies targeted against TG2 could thus contribute to the pathogenic cascade of celiac disease by increasing blood vessel permeability. 相似文献
900.