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131.
Camarero G Tyrsin OY Xiang C Pfeiffer V Pleiser S Wiese S Götz R Rapp UR 《Molecular and cellular biology》2006,26(19):7103-7115
We have previously shown that mice lacking the protein kinase B-RAF have defects in both neural and endothelial cell lineages and die around embryonic day 12 (E12). To delineate the function of B-RAF in the brain, B-RAF KIN/KIN mice lacking B-RAF and expressing A-RAF under the control of the B-RAF locus were created. B-RAF KIN/KIN embryos displayed no vascular defects, no endothelial and neuronal apoptosis, or gross developmental abnormalities, and a significant proportion of these animals survived for up to 8 weeks. Cell proliferation in the neocortex was reduced from E14.5 onwards. Newborn cortical neurons were impaired in their migration toward the cortical plate, causing a depletion of Brn-2-expressing pyramidal neurons in layers II, III, and V of the postnatal cortex. Our data reveal that B-RAF is an important mediator of neuronal survival, migration, and dendrite formation and that A-RAF cannot fully compensate for these functions. 相似文献
132.
The ability of hydrogenases isolated from Thiocapsa roseopersicina and Lamprobacter modestohalophilus to reduce metal ions and oxidize metals has been studied. Hydrogenases from both phototrophic bacteria oxidized metallic Fe, Cd, Zn and Ni into their ionic forms with simultaneous evolution of molecular hydrogen. The metal oxidation rate decreased in the series Zn>Fe>Cd>Ni and depended on the pH. The presence of methyl viologen in the reaction system accelerated this process. T. roseopersicina and L. modestohalophilus cells and their hydrogenases reduced Ni(II), Pt(IV), Pd(II) or Ru(III) to their metallic forms under H2 atmosphere. These results suggest that metals or metal ions can serve as electron donors or acceptors for hydrogenases from phototrophic bacteria. 相似文献
133.
A ureter primary explant technique, using porcine tissue sections was developed to study bystander effects under in vivo like conditions where dividing and differentiated cells are present. Targeted irradiations of ureter tissue fragments were performed with the Gray Cancer Institute charged particle microbeam at a single location (2 microm precision) with 10 3He2+ particles (5 MeV; LET 70 keV/microm). After irradiation the ureter tissue section was incubated for 7 days allowing explant outgrowth to be formed. Differentiation was estimated using antibodies to Uroplakin III, a specific marker of terminal urothelial differentiation. Even although only a single region of the tissue section was targeted, thousands of additional cells were found to undergo bystander-induced differentiation in the explant outgrowth. This resulted in an overall increase in the fraction of differentiated cells from 63.5+/-5.4% to 76.6+/-5.6%. These changes are much greater than that observed for the induction of damage in this model. One interpretation of these results is that in the tissue environment, differentiation is a much more significant response to targeted irradiation and potentially a protective mechanism. 相似文献
134.
Arun V. Holden Oleg V. Aslanidi Alan P. Benson Richard H. Clayton Graeme Halley Pan Li Wing Chiu Tong 《Journal of biological physics》2006,32(3-4):355-368
Methods for the experimental and clinical investigation of cardiac arrhythmias are limited to inferring propagation within
the myocardium, from surface measurements, or from electrodes at a few sites within the cardiac wall. Biophysically and anatomically
detailed computational models of cardiac tissues offer a powerful way for studying the electrical propagation processes and
arrhythmias within the virtual heart. We use virtual tissues to study and visualise the effects of patho- and physiological
conditions, and pharmacological interventions on transmural propagation in the virtual ventricular walls. Class III drug actions
are quantitatively explained by changes induced in the transmural dispersion of action potential duration. We illustrate the
automated construction of a virtual anisotropic ventricle from Diffusion Tensor MRI for individual hearts, and use it to explore
mechanisms leading to ventricular fibrillation. The virtual ventricular wall provides an effective tool for exploring, evaluating
and visualising processes during the initiation and maintenance of ventricular arrhythmias. 相似文献
135.
Novel tumor necrosis factor-responsive mammalian neutral sphingomyelinase-3 is a C-tail-anchored protein 总被引:2,自引:0,他引:2
Krut O Wiegmann K Kashkar H Yazdanpanah B Krönke M 《The Journal of biological chemistry》2006,281(19):13784-13793
Two genes encoding neutral sphingomyelinases-1 and -2 (sphingomyelin phosphodiesterases-2 and -3) have been recently identified that hydrolyze sphingomyelin to phosphorylcholine and ceramide. Data bank searches using a peptide sequence derived from a previously purified bovine neutral sphingomyelinase (nSMase) allowed us to identify a cDNA encoding a novel human sphingomyelinase, nSMase3, that shows only a little homology to nSMase1 and -2. nSMase3 was biochemically characterized by overexpression in a yeast strain, JK9-3ddeltaIsc1p, lacking endogenous SMase activity. Similar to nSMase2, nSMase3 is Mg2+-dependent and shows optimal activity at pH 7, which is enhanced in the presence of phosphatidylserine and inhibited by scyphostatin. nSMase3 is ubiquitously expressed as a 4.6-kb mRNA species. nSMase3 lacks an N-terminal signal peptide, yet contains a 23-amino-acid transmembrane domain close to the C terminus, which is indicative for the family of C-tail-anchored integral membrane proteins. Cellular localization studies with hemagglutinin-tagged nSMase3 demonstrated colocalization with markers of the endoplasmic reticulum as well as with Golgi markers. Tumor necrosis factor stimulates rapid activation of nSMase3 in MCF7 cells with peak activity at 1.5 min, which was impaired by expression of dominant negative FAN. 相似文献
136.
Koliasnikov OV Kiral MO Grigorenko VG Egorov AM 《Journal of bioinformatics and computational biology》2006,4(2):415-424
The third complementary determining region of the immunoglobulin heavy chain (CDR H3) is one of the more difficult structures to model due to genetic reasons. However, the conformation of proximal to beta-framework ("torso") part of the CDR H3 is very predictable. Current "CDR's canonical classes" theory is based on identifying the key positions, H94 and H101. We can determine the CDR H3 "torso" structure if arginine or lysine is present in the H94 position and/or aspartic acid in the H101 position. We target the case characterized by the absence of key residues in both the H94 and H101 positions. There has not been discussion on this case in the literature. 51 CDR H3 structures of this nature are analyzed and we established new sequence-structure rules. These rules contribute to more accurate modeling of the antibody's structure. 相似文献
137.
Specific molecular interactions mediated by the N-terminus of fibrinogen's Bbeta chain were revealed using laser tweezers-based force spectroscopy. We examined interactions between fibrinogen fragments representing the center of the molecule, NDSK, desA-NDSK, and desAB-NDSK, and two recombinant fibrinogens, gammaD364H and gammaD364A, which have nonfunctional gamma-chain polymerization sites to prevent the dominant knob-hole binding. Interactions between desA-NDSK, where the N-terminus of the Bbeta chain is present, and the fibrinogen variants showed a complex spectrum of rupture forces which disappeared with desAB-NDSK, lacking both FpA and FpB. The interactions between desA-NDSK and gammaD364H or gammaD364A were inhibited by addition of soluble FpB, but not FpA or the polymerization inhibitor peptides GPRP and GHRP. When gammaD364H fibrinogen was replaced with its X-fragment lacking alphaC- domains or with fragment D, the strongest component of the rupture force spectrum disappeared, suggesting interactions between the uncleaved FpB and the alphaC-domain. Electron microscopy confirmed the binding of desA-NDSK to either D or E regions of fibrinogen as well as to alphaC-domains. The data demonstrate the existence of weak transient interactions within and between fibrin molecules mediated by the N-terminus of the fibrinogen Bbeta chain. 相似文献
138.
The analysis of the P-selectin/PSGL-1 catch-slip bond that is periodically driven by a detaching force predicts that in the frequency range on the order of 1 s(-1) the bond lifetime undergoes significant changes with respect to both frequency and amplitude of the force. The result indicates how variations in the heart rate could have a substantial effect on leukocyte and lymphoid cell transport and adhesion to endothelial cells and platelets during inflammatory processes. 相似文献
139.
Chondroitin 6-sulfate and dextran sulfate promote hypochlorite-induced peroxidation of phosphatidylcholine liposomes 总被引:1,自引:0,他引:1
In this work, we studied whether chondroitin sulfates and dextran sulfates (DXSs) can influence hypochlorite-induced peroxidation of phosphatidylcholine (PC) liposomes. Multilamellar liposomes (2 mg lipid/ml) were prepared in phosphate buffer, pH 7.4, with NaCl or not and exposed to reagent HOCl/ClO− (1 mM) at 37 °C in the presence of different concentrations of chondroitin 6-sulfate (C6S), chondroitin 4-sulfate (C4S), DXS 8000, DXS 40,000, and DXS 500,000. Lipid peroxidation was assessed by thiobarbituric acid-reactive substance (TBARS) production. DXSs and C6S enhanced TBARS production in a dose-dependent manner. The decline in TBARS production at the relatively high C6S concentrations may be attributed to C4S present in C6S, since in contrast to C6S, C4S is known to react with hypochlorite. Dextrans, nonsulfated analogues of DXS, failed to modulate TBARS production. This fact indicates the important role of negatively charged sulfate groups for DXS to facilitate hypochlorite-induced peroxidation of PC liposomes. The electrostatic nature of the mechanism providing for the pro-oxidative effect of DXS was also supported by the influence of liposome surface charge and solution ionic strength on the extent of liposome peroxidation. The addition of calcium ions to the incubation mixture did not prevent the pro-oxidative action of DXS. The relevance of the results to atherogenesis is discussed. 相似文献
140.
The formation of chloro- and bromohydrins from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine following incubation with myeloperoxidase or eosinophil peroxidase in the presence of hydrogen peroxide, chloride and/or bromide was analysed by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry. These products were only formed below a certain pH threshold value, that increased with increasing halide concentration. Thermodynamic considerations on halide and pH dependencies of reduction potentials of all redox couples showed that the formation of a given reactive halide species in halide oxidation coupled with the reduction of compound I of heme peroxidases is only possible below a certain pH threshold that depends on halide concentration. The comparison of experimentally derived and calculated data revealed that Cl(2), Br(2), or BrCl will primarily be formed by the myeloperoxidase-H(2)O(2)-halide system. However, the eosinophil peroxidase-H(2)O(2)-halide system forms directly HOCl and HOBr. 相似文献