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991.
992.
We examined, using a Western blot technique, the contents and compositions of a specific neuronal protein, NCAM, and of an
astrocyte marker, GFAP, in the hippocampus and cortex of rats with streptozotocin (STZ)-induced diabetes and compared these
indices with those in control (intact) animals and STZ-diabetic rats treated with melatonin. Behavioral cognitive indices
manifested in the passive avoidance test (PAT) and Morris water maze (MWM) learning performance were also estimated in the
above groups of animals. As was found, STZ-diabetic rats demonstrated clear cognitive deficits according to the values of
the retention latency in the PAT and time of reaching the escape platform in the MWM performance. In these animals, the GFAP
content was elevated, and the amount of degraded products of this protein increased, as compared with the control. Simultaneously,
considerable down-regulation of the NCAM expression and modifications of NCAM isoform composition were found in diabetic animals.
In addition, significantly increased levels of lipid peroxidation (according to the amounts of malondialdehyde + 4-hydroxyalkenals)
were measured in the cortex and hippocampus of rats with stable diabetic hyperglycemia. All the above-mentioned shifts were
significantly smoothed or even nearly completely compensated in the case of treatment of STZ-diabetic rats with melatonin
(10 mg/kg per day). The role of diabetes-related changes in the amount and composition of specific neural and glial proteins
in the development of cognitive deficits, the involvement of oxidative stress in the mechanisms of the respective shifts,
and possible mechanisms of the neuroprotective effect of melatonin with respect to diabetes-related pathological biochemical
and behavioral shifts are discussed.
Neirofiziologiya/Neurophysiology, Vol. 40, No. 2, pp. 105–111, March–April, 2008. 相似文献
993.
Bechara A Nawabi H Moret F Yaron A Weaver E Bozon M Abouzid K Guan JL Tessier-Lavigne M Lemmon V Castellani V 《The EMBO journal》2008,27(11):1549-1562
Axonal receptors for class 3 semaphorins (Sema3s) are heterocomplexes of neuropilins (Nrps) and Plexin-As signalling coreceptors. In the developing cerebral cortex, the Ig superfamily cell adhesion molecule L1 associates with Nrp1. Intriguingly, the genetic removal of L1 blocks axon responses of cortical neurons to Sema3A in vitro despite the expression of Plexin-As in the cortex, suggesting either that L1 substitutes for Plexin-As or that L1 and Plexin-A are both required and mediate distinct roles. We report that association of Nrp1 with L1 but not Plexin-As mediates the recruitment and activation of a Sema3A-induced focal adhesion kinase-mitogen-activated protein kinase cascade. This signalling downstream of L1 is needed for the disassembly of adherent points formed in growth cones and subsequently their collapse response to Sema3A. Plexin-As and L1 are coexpressed and present in common complexes in cortical neurons and both dominant-negative forms of Plexin-A and L1 impair their response to Sema3A. Consistently, Nrp1-expressing cortical projections are defective in mice lacking Plexin-A3, Plexin-A4 or L1. This reveals that specific signalling activities downstream of L1 and Plexin-As cooperate for mediating the axon guidance effects of Sema3A. 相似文献
994.
Lehembre F Yilmaz M Wicki A Schomber T Strittmatter K Ziegler D Kren A Went P Derksen PW Berns A Jonkers J Christofori G 《The EMBO journal》2008,27(19):2603-2615
Loss of expression of the cell-cell adhesion molecule E-cadherin is a hallmark of epithelial-mesenchymal transition (EMT) in development and in the progression from epithelial tumours to invasive and metastatic cancers. Here, we demonstrate that the loss of E-cadherin function upregulates expression of the neuronal cell adhesion molecule (NCAM). Subsequently, a subset of NCAM translocates from fibroblast growth factor receptor (FGFR) complexes outside lipid rafts into lipid rafts where it stimulates the non-receptor tyrosine kinase p59(Fyn) leading to the phosphorylation and activation of focal adhesion kinase and the assembly of integrin-mediated focal adhesions. Ablation of NCAM expression during EMT inhibits focal adhesion assembly, cell spreading and EMT. Conversely, forced expression of NCAM induces epithelial cell delamination and migration, and high NCAM expression correlates with tumour invasion. These results establish a mechanistic link between the loss of E-cadherin expression, NCAM function, focal adhesion assembly and cell migration and invasion. 相似文献
995.
Mutations in mitochondrial small subunit ribosomal proteins MRPS16 or MRPS22 cause severe, fatal respiratory chain dysfunction due to impaired translation of mitochondrial mRNAs. The loss of either MRPS16 or MRPS22 was accompanied by the loss of most of another small subunit protein MRPS11. However, MRPS2 was reduced only about 2-fold in patient fibroblasts. This observation suggests that the small ribosomal subunit is only partially able to assemble in these patients. Two large subunit ribosomal proteins, MRPL13 and MRPL15, were present in substantial amounts suggesting that the large ribosomal subunit is still present despite a non-functional small subunit. 相似文献
996.
The reaction of aged carboplatin (reaction of carboplatin in 24 mM NaHCO(3) for 45 h, 37 degrees, pH 8.6) with pBR322 DNA at 0 < r < 2.8, where r = [drug]/[DNA-bp], in 24 mM HEPES buffer, pH 7.4, for 24 h, followed by agarose gel electrophoresis showed DNA mobility changes consistent with unwinding closed circular DNA. However, identical experiments conducted in a two-buffer system, 24 mM HEPES plus 24 mM carbonate, showed no DNA mobility changes, indicating that carbonate blocks formation of the 1,2 intrastrand cross-link on DNA. Studies with aged carboplatin and with cisplatin carried out with ca. 4.0 < r < 10.0 in the two-buffer system show that some DNA binding and unwinding occurs for both drugs. Since carbonate inhibits the binding of aged carboplatin and cisplatin to DNA, carbonate present in the body likely modulates the reactivity of these drugs with a variety of biological targets including DNA. 相似文献
997.
Ashraf SM Berger I Nazarov AA Hartinger CG Koroteev MP Nifant'ev EE Keppler BK 《化学与生物多样性》2008,5(8):1640-1644
The synthesis of metal complexes with bioligands is one option to introduce chirally defined ligands to catalysts. Herein, the hydration of nitriles to the corresponding carboxamides by use of ruthenium(II) complexes is described, which were obtained by attaching derivatives of the 3,5,6-bicyclophosphite-alpha-D-glucofuranoside ligand. 相似文献
998.
Roess DA Smith SM Winter P Zhou J Dou P Baruah B Trujillo AM Levinger NE Yang X Barisas BG Crans DC 《化学与生物多样性》2008,5(8):1558-1570
There is increasing evidence for the involvement of plasma membrane microdomains in insulin receptor function. Moreover, disruption of these structures, which are typically enriched in sphingomyelin and cholesterol, results in insulin resistance. Treatment strategies for insulin resistance include the use of vanadium (V) compounds which have been shown in animal models to enhance insulin responsiveness. One possible mechanism for insulin-enhancing effects might involve direct effects of V compounds on membrane lipid organization. These changes in lipid organization promote the partitioning of insulin receptors and other receptors into membrane microdomains where receptors are optimally functional. To explore this possibility, we have used several strategies involving V complexes such as [VO(2)(dipic)](-) (pyridin-2,6-dicarboxylatodioxovanadium(V)), decavanadate (V(10)O(28)(6-), V(10)), BMOV (bis(maltolato)oxovanadium(IV)), and [VO(saltris)](2) (2-salicylideniminato-2-(hydroxymethyl)-1,3-dihydroxypropane-oxovanadium(V)). Our strategies include an evaluation of interactions between V-containing compounds and model lipid systems, an evaluation of the effects of V compounds on lipid fluidity in erythrocyte membranes, and studies of the effects of V-containing compounds on signaling events initiated by receptors known to use membrane microdomains as signaling platforms. 相似文献
999.
Twenty-eight [6-(aminomethyl)nicotinate]dichloridoplatinum(II) complexes 1 esterified with various terpene alcohols either directly or via alkyl spacers were tested for antiproliferative activity in human 518A2 melanoma and HL-60 leukemia cells. Generally, conjugates with menthanes and polycyclic sesquiterpenes attached via propane-1,2-diyl spacers were most active. In the melanoma cells, the propane-1,2-diyl-spacered conjugates of (-)-menthol (1a(2')), (+)-neomenthol (1b(2')), (-)-carvomenthol (1h(2')), and (-)-isolongifolol (1n(2')) displayed growth inhibition at IC(50)<4 microM which is ten times smaller than that of cisplatin. The stationary diamino ligand was also crucial. The (-)-menthyl ester complexes with 2,3-diaminopropanoate (9a) and 2,4-diaminobutanoate (10a) ligands caused a greater and persistent growth inhibition in HT-29 colon cancer cells upon long-term exposure when compared to the 6-(aminomethyl)nicotinate analogue 1a. The cedrenyl ester 1l and the menthoxyisopropyl ester 1a(2') proved most efficacious in all three tumor cell lines. The DNA binding of complexes 1 was assessed by electrophoretic band-shift experiments and found correlated to the terpene structure but not to the observed antiproliferative activities. 相似文献
1000.
Liposomal formulations of dinuclear cluster rhenium (Re) compounds were used in biochemical trials. Interaction of liposomal forms of some Re compounds with red blood cells in experiments in vitro showed strong cell-stabilizing properties. In the models of tumor growth and hemolytic anemia in vivo, liposomal forms had better therapeutic effects in comparison with their solutions. The process of formation of liposomes of cluster Re compounds with different organic ligands was investigated by the method of electronic absorption spectra and mechanism of their interactions with lipids is proposed. Encapsulation of cluster Re compounds to lipid coating may have activation significance for the quadruple Re-Re bond. 相似文献