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71.
Mareuil F Sizun C Perez J Schoenauer M Lallemand JY Bontems F 《European biophysics journal : EBJ》2007,37(1):95-104
Most proteins comprise several domains and/or participate in functional complexes. Owing to ongoing structural genomic projects,
it is likely that it will soon be possible to predict, with reasonable accuracy, the conserved regions of most structural
domains. Under these circumstances, it will be important to have methods, based on simple-to-acquire experimental data, that
allow to build and refine structures of multi-domain proteins or of protein complexes from homology models of the individual
domains/proteins. It has been recently shown that small angle X-ray scattering (SAXS) and NMR residual dipolar coupling (RDC)
data can be combined to determine the architecture of such objects when the X-ray structures of the domains are known and
can be considered as rigid objects. We developed a simple genetic algorithm to achieve the same goal, but by using homology
models of the domains considered as deformable objects. We applied it to two model systems, an S1KH bi-domain of the NusA
protein and the γS-crystallin protein. Despite its simplicity our algorithm is able to generate good solutions when driven
by SAXS and RDC data. 相似文献
72.
Afonso PV Ozden S Prevost MC Schmitt C Seilhean D Weksler B Couraud PO Gessain A Romero IA Ceccaldi PE 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(4):2576-2583
The blood-brain barrier (BBB), which constitutes the interface between blood and cerebral parenchyma, has been shown to be disrupted during retroviral associated neuromyelopathies. Human T cell leukemia virus (HTLV-1)-associated myelopathy/tropical spastic paraparesis is a slowly progressive neurodegenerative disease, in which evidence of BBB breakdown has been demonstrated by the presence of lymphocytic infiltrates in the CNS and plasma protein leakage through cerebral endothelium. Using an in vitro human BBB model, we investigated the cellular and molecular mechanisms involved in endothelial changes induced by HTLV-1-infected lymphocytes. We demonstrate that coculture with infected lymphocytes induces an increase in paracellular endothelial permeability and transcellular migration, via IL-1alpha and TNF-alpha secretion. This disruption is associated with tight junction disorganization between endothelial cells, and alterations in the expression pattern of tight junction proteins such as zonula occludens 1. These changes could be prevented by inhibition of the NF-kappaB pathway or of myosin light chain kinase activity. Such disorganization was confirmed in histological sections of spinal cord from an HTLV-1-associated myelopathy/tropical spastic paraparesis patient. Based on this BBB model, the present data indicate that HTLV-1-infected lymphocytes can induce BBB breakdown and may be responsible for the CNS infiltration that occurs in the early steps of retroviral-associated neuromyelopathies. 相似文献
73.
74.
Ploquin M Petukhova GV Morneau D Déry U Bransi A Stasiak A Camerini-Otero RD Masson JY 《Nucleic acids research》2007,35(8):2719-2733
Genetic analysis of fission yeast suggests a role for the spHop2–Mnd1 proteins in the Rad51 and Dmc1-dependent meiotic recombination pathways. In order to gain biochemical insights into this process, we purified Schizosaccharomyces pombe Hop2-Mnd1 to homogeneity. spHop2 and spMnd1 interact by co-immunoprecipitation and two-hybrid analysis. Electron microscopy reveals that S. pombe Hop2–Mnd1 binds single-strand DNA ends of 3′-tailed DNA. Interestingly, spHop2-Mnd1 promotes the renaturation of complementary single-strand DNA and catalyses strand exchange reactions with short oligonucleotides. Importantly, we show that spHop2-Mnd1 stimulates spDmc1-dependent strand exchange and strand invasion. Ca2+ alleviate the requirement for the order of addition of the proteins on DNA. We also demonstrate that while spHop2-Mnd1 affects spDmc1 specifically, mHop2 or mHop2-Mnd1 stimulates both the hRad51 and hDmc1 recombinases in strand exchange assays. Thus, our results suggest a crucial role for S. pombe and mouse Hop2-Mnd1 in homologous pairing and strand exchange and reveal evolutionary divergence in their specificity for the Dmc1 and Rad51 recombinases. 相似文献
75.
Temperini C Winum JY Montero JL Scozzafava A Supuran CT 《Bioorganic & medicinal chemistry letters》2007,17(10):2795-2801
N-Hydroxysulfamide is a 2000-fold more potent inhibitor of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1) as compared to sulfamide. It also inhibits other physiologically relevant isoforms, such as the tumor-associated CA IX and XII (K(I)s in the range of 0.865-1.34microM). In order to understand the binding of this inhibitor to the enzyme active site, the X-ray crystal structure of the human hCA II-N-hydroxysulfamide adduct was resolved. The inhibitor coordinates to the active site zinc ion by the ionized primary amino group, participating in an extended network of hydrogen bonds with amino acid residues Thr199, Thr200 and two water molecules. The additional two hydrogen bonds in which N-hydroxysulfamide bound to hCA II is involved as compared to the corresponding adduct of sulfamide may explain its higher affinity for the enzyme, also providing hints for the design of tight-binding CA inhibitors possessing an organic moiety substituting the NH group in the N-hydroxysulfamide structure. 相似文献
76.
Winum JY Thiry A Cheikh KE Dogné JM Montero JL Vullo D Scozzafava A Masereel B Supuran CT 《Bioorganic & medicinal chemistry letters》2007,17(10):2685-2691
A series of aromatic/heterocyclic sulfonamides incorporating 2,3:4,5-bis-O-(isopropylidene)-beta-d-fructopyranosyl-thioureido moieties has been synthesized and assayed for the inhibition of seven human isoforms of the zinc enzyme carbonic anhydrase (hCA, EC 4.2.1.1). The new derivatives behaved as weak hCA I inhibitors (K(I)s of 9.4 -13.3microM), were efficient hCA II inhibitors (K(I)s of 6-750nM), and slightly inhibited isoforms hCA IV and hCA VA. Only the sulfanilamide derivative showed efficient and selective inhibition of hCA IV (K(I) of 10nM). These derivatives also showed excellent hCA VII inhibitory activity (K(I)s of 10-79nM), being less efficient as inhibitors of the transmembrane isoforms hCA IX (K(I)s of 10-4500nM) and hCA XIV (K(I)s of 21-3500nM). Two of the new compounds showed anticonvulsant action in a maximal electroshock seizure test in mice, with the fluorosulfanilamide derivative being a more efficient anticonvulsant than the antiepileptic drug topiramate. 相似文献
77.
Charniot JC Bonnefont-Rousselot D Albertini JP Zerhouni K Dever S Richard I Nataf P Pavie A Monsuez JJ Delattre J Artigou JY 《Free radical research》2007,41(8):911-918
Xenotransplantation (XT) reveals a growing interest for the treatment of cardiomyopathy. The major barrier is an acute vascular rejection due to an acute humoral rejection. This pathogenesis is a difficult issue and in order to elaborate means for its prevention, we analysed the implication of oxidative stress (OS) on hearts from mini-pigs followed by reperfusion with either autologous or human blood in an attempt to simulate xenotransplantation. About 14 hearts were studied after a Langendorff blood reperfusion: allografts with autologous blood (n = 7) or xenografts with human blood (n = 7). Blood samples were drawn from the coronary sinus to assess ischemia and OS. In xenografts, arrhythmias occurred more frequently (p < 0.01, left ventricular systolic pressure decreased more significantly (p < 0.05), thiobarbituric acid-reactive substances concentrations increased at 30 min (0.7 +/- 0.1 vs. 2.4 +/- 0.3 mmol/l; p < 0.05) while vitamin A levels decreased (p < 0.05). XT was associated with a significant increase in ischemic injury and OS production. OS might play an eminent role in hyperacute humoral rejection. 相似文献
78.
79.
Davit-Béal T Chisaka H Delgado S Sire JY 《Biological reviews of the Cambridge Philosophical Society》2007,82(1):49-81
Elucidation of the mechanisms controlling early development and organogenesis is currently progressing in several model species and a new field of research, evolutionary developmental biology, which integrates developmental and comparative approaches, has emerged. Although the expression pattern of many genes during tooth development in mammals is known, data on other lineages are virtually non-existent. Comparison of tooth development, and particularly of gene expression (and function) during tooth morphogenesis and differentiation, in representative species of various vertebrate lineages is a prerequisite to understand what makes one tooth different from another. Amphibians appear to be good candidates for such research for several reasons: tooth structure is similar to that in mammals, teeth are renewed continuously during life (=polyphyodonty), some species are easy to breed in the laboratory, and a large amount of morphological data are already available on diverse aspects of tooth biology in various species. The aim of this review is to evaluate current knowledge on amphibian teeth, principally concerning tooth development and replacement (including resorption), and changes in morphology and structure during ontogeny and metamorphosis. Throughout this review we highlight important questions which remain to be answered and that could be addressed using comparative morphological studies and molecular techniques. We illustrate several aspects of amphibian tooth biology using data obtained for the caudate Pleurodeles waltl. This salamander has been used extensively in experimental embryology research during the past century and appears to be one of the most favourable amphibian species to use as a model in studies of tooth development. 相似文献
80.
Thomas?Durand Sophie?Jacob Laura?Lebouil Hassen?Douzane Philippe?Lestaevel Amithys?Rahimian Dimitri?Psimaras Lo?c?Feuvret Delphine?Leclercq Bruno?Brochet Radia?Tamarat Fabien?Milliat Marc?Benderitter Nicolas?Vayatis Georges?No?l Khê?Hoang-Xuan Jean-Yves?Delattre Damien?Ricard Marie-Odile?BernierEmail author 《BMC neurology》2015,15(1):261