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951.
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Laura Zaccaro Enrico Bucci Rosa Maria Vitale Giuseppe Perretta Roberto Fattorusso Ettore Benedetti Michele Saviano Carlo Pedone 《Journal of peptide science》2003,9(2):90-105
The objective of our study was to mimic in a typical reductionist approach the molecular interactions observed at the interface between the gp130 receptor and interleukin-6 during formation of their complex. A peptide system obtained by reproducing some of the interleukin-6/gp130 molecular interactions into a two-helix bundle structure was investigated. The solution conformational features of this system were determined by CD and NMR techniques. The CD titration experiments demonstrated that the interaction between the designed peptides is specific and based on a well-defined stoichiometry. The NMR data confirmed some of the structural features of the binding mechanism as predicted by the rational design and indicated that under our conditions the recognition specificity and affinity can be explained by the formation of a two-helix bundle. Thus, the data reported herein represent a promising indication on how to develop new peptides able to interfere with formation of the interleukin-6/gp130 complex. 相似文献
954.
Giovanni Triolo Antonina Accardo-Palumbo Francesco Dieli Francesco Ciccia Angelo Ferrante Ennio Giardina Di Caterina Sano Giuseppe Licata 《Arthritis research & therapy》2003,5(5):R262
Beh?et's disease is a multisystem disease in which there is evidence of immunological dysregulation. It has been proposed
that γ/δ T cells are involved in its pathogenesis. The aim of the present study was to assess the capacity of γ/δ T cells
with phenotype Vγ9/Vδ2, from a group of Italian patients with Beh?et's disease, to proliferate in the presence of various
phosphoantigens and to express tumour necrosis factor (TNF) and IL-12 receptors. Twenty-five patients and 45 healthy individuals
were studied. Vγ9/Vδ2 T cells were analyzed by fluorescence activated cell sorting, utilizing specific monoclonal antibodies.
For the expansion of Vγ9/Vδ2 T cells, lymphocytes were cultured in the presence of various phosphoantigens. The expression
of TNF receptor II and IL-12 receptor β1 was evaluated with the simultaneous use of anti-TNF receptor II phycoerythrin-labelled (PE) or anti-IL-12 receptor β1 PE and anti-Vδ2 T-cell receptor fluorescein isothiocyanate. There was a certain hierarchy in the response of Vγ9/Vδ2 T cells
toward the different phosphoantigens, with the highest expansion factor obtained with dimethylallyl pyrophosphate and the
lowest with xylose 1P. The expansion factor was fivefold greater in patients with active disease than in those with inactive
disease or in control individuals. TNF receptor II and IL-12 receptor β1 expressions were increased in both patients and control individuals. The proportion of Vγ9/Vδ2 T cells bearing these receptors
was raised in active disease when Vγ9/Vδ2 T cells were cultured in the presence of dimethylallyl pyrophosphate. These results
indicate that Vγ9/Vδ2 T cell activation is correlated with disease progression and probably involved in the pathogenesis. 相似文献
955.
Patrizio Dimitri Ruggiero Caizzi Ennio Giordano Maria Carmela Accardo Giovanna Lattanzi Giuseppe Biamonti 《Chromosoma》2009,118(4):419-435
The organization of chromosomes into euchromatin and heterochromatin is amongst the most important and enigmatic aspects of
genome evolution. Constitutive heterochromatin is a basic yet still poorly understood component of eukaryotic chromosomes,
and its molecular characterization by means of standard genomic approaches is intrinsically difficult. Although recent evidence
indicates that the presence of transcribed genes in constitutive heterochromatin is a conserved trait that accompanies the
evolution of eukaryotic genomes, the term heterochromatin is still considered by many as synonymous of gene silencing. In
this paper, we comprehensively review data that provide a clearer picture of transcribed sequences within constitutive heterochromatin,
with a special emphasis on Drosophila and humans. 相似文献
956.
957.
Anna Valenti Giuseppe Perugino Takehiko Nohmi Mos Rossi Maria Ciaramella 《Nucleic acids research》2009,37(13):4287-4295
Reverse gyrase is a unique DNA topoisomerase endowed with ATP-dependent positive supercoiling activity. It is typical of microorganisms living at high temperature and might play a role in maintenance of genome stability and repair. We have identified the translesion DNA polymerase SsoPolY/Dpo4 as one partner of reverse gyrase in the hyperthermophilic archaeon Sulfolobus solfataricus. We show here that in cell extracts, PolY and reverse gyrase co-immunoprecipitate with each other and with the single strand binding protein, SSB. The interaction is confirmed in vitro by far-western and Surface Plasmon Resonance. In functional assays, reverse gyrase inhibits PolY, but not the S. solfataricus B-family DNA polymerase PolB1. Mutational analysis shows that inhibition of PolY activity depends on both ATPase and topoisomerase activities of reverse gyrase, suggesting that the intact positive supercoiling activity is required for PolY inhibition. In vivo, reverse gyrase and PolY are degraded after induction of DNA damage. Inhibition by reverse gyrase and degradation might act as a double mechanism to control PolY and prevent its potentially mutagenic activity when undesired. Inhibition of a translesion polymerase by topoisomerase-induced modification of DNA structure may represent a previously unconsidered mechanism of regulation of these two-faced enzymes. 相似文献
958.
Giuseppe Grasso Ashley I. Bush Roberta D’Agata Enrico Rizzarelli Giuseppe Spoto 《European biophysics journal : EBJ》2009,38(4):407-414
Solid-support based assays offer several advantages that are not normally available in solution. Enzymes that are anchored
on gold surfaces can interact with several different molecules, opening the way to high throughput array format based assays.
In this scenario, surface plasmon resonance (SPR) and mass spectrometry (MS) investigations have often been applied to analyze
the interaction between immobilized enzyme and its substrate molecules in a tag-free environment. Here, we propose a SPR-MS
combined experimental approach aimed at studying insulin degrading enzyme (IDE) immobilized onto gold surfaces and its ability
to interact with insulin. The latter is delivered by a microfluidic system to the IDE functionalized surface and the activity
of the immobilized enzyme is verified by atmospheric pressure/matrix assisted laser desorption ionization (AP/MALDI) MS analysis.
The SPR experiments allow the calculation of the kinetic constants involved for the interaction between immobilized IDE and
insulin molecules and evidence of IDE conformational change upon insulin binding is also obtained. 相似文献
959.
Giuseppe Cassano Giuseppe Gasparre Mauro Niso Marialessandra Contino Vito Scalera Nicola Antonio Colabufo 《Cell calcium》2009,45(4):340-345
We demonstrate that F281, a synthetic agonist of the sigma-2 receptor (s2R), induces a non transient increase in intracellular [Ca2+] ([Ca2+]i) and cell death in SK-N-SH cells. Sigma receptors are classified into two subtypes, with different molecular weight and tissue distribution. While the sigma-1 receptor has been cloned, the s2r is less characterized and its physiological ligand and role need further investigation. In tumour cell lines, synthetic agonists of the s2R trigger apoptosis and modulate [Ca2+]i. In particular, CB-64D induces a Ca2+ response while PB28 supresses Ca2+ signalling. We have recently synthesized F281, by replacing the 5-methoxytetraline moiety of PB28 with a carbazole nucleus. Although this bioisosteric substitution should not affect the ligand affinity at the receptor, F281 (after 24 h incubation) was more cytotoxic than PB28 (EC50 values 65.4 nM and 8.13 μM, respectively) in SK-N-SH cells. We used the fluorescent probes fura-2, rhod-2 and JC-1. F281 mobilizes Ca2+ from mitochondria and from the endoplasmic reticulum, by opening its inositol 1,4,5-trisphosphate receptor; Ca2+-entry through the channels activated by store depletion was also observed. After the increase in [Ca2+]i and within 10 min, we observed a sudden drop in metabolic activity and intracellular [ATP] leading to cell death. 相似文献
960.
Diego La Mendola Serena Caminati Salvatore S. Emmi Giuseppe Maccarrone Adriana Pietropaolo 《Journal of inorganic biochemistry》2009,103(2):195-204
Potentiometric and spectroscopic (UV-Vis, CD and EPR) studies were carried out on copper(II) complexes with chicken prion protein N-terminal fragments, Ac-(PHNPGY)4-NH2, and the mutated residue, Ac-(PHNPGF)4-NH2, to assess the role of tyrosine in the copper coordination. Both thermodynamic and spectroscopic results indicate that chicken prion fragments are not able to bind more than two copper ions and only with the involvement of side chain tyrosine groups. The prevailing complex shows one copper ion bound to four imidazole nitrogen atoms in the 1:1 metal to ligand ratio systems. The superoxide dismutase (SOD)-like activity of copper(II) complexes with the avian peptides and mammal analogue, Ac-(PHGGGWGQ)4-NH2, was also investigated by means of Pulse radiolysis. The copper(II) complexes with avian peptides do not display SOD-like activity, while very low activity has been detected for the copper(II) complexes with mammalian tetraoctarepeat. 相似文献