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101.
CHRISTOPHE GONINDARD CATHERINE GOIGOUX ETIENNE HOLLANDE LUCIEN DUSSOURD D'HINTERLAND 《Pigment cell & melanoma research》1996,9(3):148-153
The injection of α-MSH or of one of its analogues ([Nle4-D.Phe7] α-MSH4–10) reduced, in vivo, the release of two cytokines (IL-1α and TNFα) involved in inflammation. The inflammatory state was induced in BALB/c mice by intraperitoneal injection of a sublethal dose of lipopolysaccharides (LPS). The assay of these cytokines by ELISA showed a reduction of 20% with α-MSH and between 30 and 60% with the α-MSH analogue. The α-MSH or the analogue was administered in one of two ways: intravenously or subcutaneously. The most efficient method seemed to be the subcutaneous one because it improved the activity 10,000 times more than the intravenous method. Moreover, the analogue induced a regression of mortality in the animals treated by the intravenous method. Our results show that α-MSH and one of its analogues inhibit IL-1α and TNFα, and can be used as anti-inflammatory molecules. 相似文献
102.
《Journal of molecular biology》2022,434(23):167872
EF-hand Ca2+-binding proteins (CBPs), such as S100 proteins (S100s) and calmodulin (CaM), are signaling proteins that undergo conformational changes upon increasing intracellular Ca2+. Upon binding Ca2+, S100 proteins and CaM interact with protein targets and induce important biological responses. The Ca2+-binding affinity of CaM and most S100s in the absence of target is weak (CaKD > 1 μM). However, upon effector protein binding, the Ca2+ affinity of these proteins increases via heterotropic allostery (CaKD < 1 μM). Because of the high number and micromolar concentrations of EF-hand CBPs in a cell, at any given time, allostery is required physiologically, allowing for (i) proper Ca2+ homeostasis and (ii) strict maintenance of Ca2+-signaling within a narrow dynamic range of free Ca2+ ion concentrations, [Ca2+]free. In this review, mechanisms of allostery are coalesced into an empirical “binding and functional folding (BFF)” physiological framework. At the molecular level, folding (F), binding and folding (BF), and BFF events include all atoms in the biomolecular complex under study. The BFF framework is introduced with two straightforward BFF types for proteins (type 1, concerted; type 2, stepwise) and considers how homologous and nonhomologous amino acid residues of CBPs and their effector protein(s) evolved to provide allosteric tightening of Ca2+ and simultaneously determine how specific and relatively promiscuous CBP-target complexes form as both are needed for proper cellular function. 相似文献
103.
Xian Zeng Hui Zhao Yubin Li Jiajun Fan Yun Sun Shaofei Wang Ziyu Wang Ping Song Dianwen Ju 《Autophagy》2015,11(2):355-372
The frontline tyrosine kinase inhibitor (TKI) imatinib has revolutionized the treatment of patients with chronic myeloid leukemia (CML). However, drug resistance is the major clinical challenge in the treatment of CML. The Hedgehog (Hh) signaling pathway and autophagy are both related to tumorigenesis, cancer therapy, and drug resistance. This study was conducted to explore whether the Hh pathway could regulate autophagy in CML cells and whether simultaneously regulating the Hh pathway and autophagy could induce cell death of drug-sensitive or -resistant BCR-ABL+ CML cells. Our results indicated that pharmacological or genetic inhibition of Hh pathway could markedly induce autophagy in BCR-ABL+ CML cells. Autophagic inhibitors or ATG5 and ATG7 silencing could significantly enhance CML cell death induced by Hh pathway suppression. Based on the above findings, our study demonstrated that simultaneously inhibiting the Hh pathway and autophagy could markedly reduce cell viability and induce apoptosis of imatinib-sensitive or -resistant BCR-ABL+ cells. Moreover, this combination had little cytotoxicity in human peripheral blood mononuclear cells (PBMCs). Furthermore, this combined strategy was related to PARP cleavage, CASP3 and CASP9 cleavage, and inhibition of the BCR-ABL oncoprotein. In conclusion, this study indicated that simultaneously inhibiting the Hh pathway and autophagy could potently kill imatinib-sensitive or -resistant BCR-ABL+ cells, providing a novel concept that simultaneously inhibiting the Hh pathway and autophagy might be a potent new strategy to overcome CML drug resistance. 相似文献
104.
M. V. Achi J. M. Figueroa V. González Nicolini M. J. Villar J. H. Tramezzani 《Cell and tissue research》1995,281(2):375-378
The presence and distribution of peptidergic nerve fibers were studied in the testis and mesorchium of the toad by means of immunohistochemistry. Cryostat sections of the testis and whole-mount preparations of mesorchia were immunostained with antisera to calcitonin gene-related peptide (CGRP) and neuropeptide tyrosine (NPY). After leaving the mesorchium CGRP-immunoreactive (IR) fibers were seen predominantly running in between the seminiferous tubules. In addition, a small population of CGRP-IR nerve fibers formed thin plexuses around blood vessels. Conversely, NPY-like immunoreactivity predominated in nerve fibers that formed dense plexuses around vessels both in the mesorchium and testis. Additionally, some single NPY-IR nerve fibers could be seen in both structures studied. The functional significance of these peptidergic systems in the testis of the toad remains to be analyzed. 相似文献
105.
Neuropathic pruritus conditions arise from structural and/or functional damage of the peripheral or central nervous system. Novel findings of pruritus specific mediators and pathways strengthen the specificity theory of pruritus transmission, however electrophysiological studies suggest that focal activation of nociceptors and distinct discharge patterns of primary afferents also contribute to the development of the sensation of pruritus. A complex interplay between excitatory and inhibitory interneurons at spinal level, non-neuronal cells and descending modulation from upper centers contributes to neuronal sensitization and clinically to the chronicity of pruritus, as well as accompanying phenomena such as alloknesis and hyperknesis. Several topical, systemic and non-pharmacological therapeutic approaches directed at distinct targets are currently available. 相似文献
106.
《Bioorganic & medicinal chemistry letters》2014,24(7):1820-1824
The design and synthesis of a series of novel tricyclic IAP inhibitors is reported. Rapid assembly of the core tricycle involved two key steps: Rh-catalyzed hydrogenation of an unsaturated bicyclic ring system and a Ru-catalyzed ring closing alkene metathesis reaction. The final Smac mimetics bind to cIAP1 and XIAP BIR3 domains and elicit the desired phenotype in cellular proliferation assays. Dimeric IAP inhibitors were found to possess nanomolar potency in a cellular proliferation assay and favourable in vitro drug-like properties. 相似文献
107.
108.
《Expert review of proteomics》2013,10(2):125-128
Evaluation of: Stephanowitz H, Lange S, Lang D et al. Improved two-dimensional reversed phase–reversed phase LC-MS/MS approach for identification of peptide–protein interactions. J. Proteome Res. 11(2), 1175–1183 (2011).Recent developments in bottom-up proteomics have supplanted the use of gel-based approaches in favor of multidimensional chromatographic separations of peptide mixtures followed by mass spectrometry analysis. This trend is driven by the desire to eliminate labor-intensive in-gel digestion procedures and increase proteome coverage through better recovery of proteolytic fragments. Introduction of reversed-phase–reversed-phase 2D separation techniques is one of the major improvements that have made this possible. In this article, we review recent developments in 2D HPLC and highlight variations in reversed-phase HPLC separation selectivity that allow for superior peak capacity in peptide fractionation. 相似文献
109.
110.