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Gasser B Maurer M Gach J Kunert R Mattanovich D 《Biotechnology and bioengineering》2006,94(2):353-361
34.
Eiben S Kaysser L Maurer S Kühnel K Urlacher VB Schmid RD 《Journal of biotechnology》2006,124(4):662-669
Isolated P450 monooxygenases have for long been neglected catalysts in enzyme technology. This is surprising as they display a remarkable substrate specificity catalyzing reactions, which represent a challenge for classic organic chemistry. On the other hand, many P450 monooxygenases are membrane bound, depend on rather complicated electron transfer systems and require expensive cofactors such as NAD(P)H. Their activities are low, and stability leaves much to be desired. The use of bacterial P450 monooxygenases from CYP102 family allows overcoming some of these handicaps. They are soluble and their turnovers are high, presumably because their N-terminal heme monooxygenase and their C-terminal diflavin reductase domain are covalently linked. In recent years, protein engineering approaches have been successfully used to turn CYP102 monooxgenases into powerful biocatalysts. 相似文献
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Stephen?R.F. Twigg Deborah Lloyd Dagan Jenkins Nursel?E. El?ioglu Christopher?D.O. Cooper Nouriya Al-Sannaa Ali Annagür Gabriele Gillessen-Kaesbach Irina Hüning Samantha?J.L. Knight Judith?A. Goodship Bernard?D. Keavney Philip?L. Beales Opher Gileadi Simon?J. McGowan Andrew?O.M. Wilkie 《American journal of human genetics》2012,91(5):897-905
Carpenter syndrome is an autosomal-recessive multiple-congenital-malformation disorder characterized by multisuture craniosynostosis and polysyndactyly of the hands and feet; many other clinical features occur, and the most frequent include obesity, umbilical hernia, cryptorchidism, and congenital heart disease. Mutations of RAB23, encoding a small GTPase that regulates vesicular transport, are present in the majority of cases. Here, we describe a disorder caused by mutations in multiple epidermal-growth-factor-like-domains 8 (MEGF8), which exhibits substantial clinical overlap with Carpenter syndrome but is frequently associated with abnormal left-right patterning. We describe five affected individuals with similar dysmorphic facies, and three of them had either complete situs inversus, dextrocardia, or transposition of the great arteries; similar cardiac abnormalities were previously identified in a mouse mutant for the orthologous Megf8. The mutant alleles comprise one nonsense, three missense, and two splice-site mutations; we demonstrate in zebrafish that, in contrast to the wild-type protein, the proteins containing all three missense alterations provide only weak rescue of an early gastrulation phenotype induced by Megf8 knockdown. We conclude that mutations in MEGF8 cause a Carpenter syndrome subtype frequently associated with defective left-right patterning, probably through perturbation of signaling by hedgehog and nodal family members. We did not observe any subject with biallelic loss-of function mutations, suggesting that some residual MEGF8 function might be necessary for survival and might influence the phenotypes observed. 相似文献
37.
Toluene diisocyanates (2,4-TDI and 2,6-TDI) are important intermediates in the chemical industry. Among the main damages after low levels of TDI exposure are lung sensitization and asthma. It is therefore necessary to have sensitive and specific methods to monitor isocyanate exposure of workers. Urinary metabolites or protein adducts have been used as biomarkers in workers exposed to TDI. However, with these methods it was not possible to determine if the biomarkers result from exposure to TDI or to the corresponding toluene diamines (TDA). This work presents a new procedure for the determination of isocyanate-specific albumin adducts. Isotope dilution mass spectrometry was used to measure the adducts in albumin present in workers exposed to TDI. 2,4-TDI and 2,6-TDI formed adducts with lysine: N(?)-[({3-amino-4-methylphenyl}amino)carbonyl]-lysine, N(?)-[({5-amino-2-methylphenyl}amino)carbonyl]-lysine, and N(?)- [({3-amino-2-methylphenyl}amino)carbonyl]-lysine. In future studies, this new method can be applied to measure TDI-exposures in workers. 相似文献
38.
To identify proteins that are involved in RNA degradation and processing in Halobacterium sp. NRC-1, we purified proteins with RNA-degrading activity by classical biochemical techniques. One of these proteins showed strong homology to the eukaryotic initiation factor 5A (eIF-5A) and was accordingly named archaeal initiation factor 5A (aIF-5A). Eukaryotic IF-5A is known to be involved in mRNA turnover and to bind RNA. Hypusination of eIF-5A is required for sequence-specific binding of RNA. This unique post-translational modification is restricted to Eukarya and Archaea. The exact function of eIF-5A in RNA turnover remained obscure. Here we show for the first time that aIF-5A from Halobacterium sp. NRC-1 exhibits RNA cleavage activity, preferentially cleaving adjacent to A nucleotides. Detectable RNA binding could be shown for aIF-5A purified from Halobacterium sp. NRC-1 but not from Escherichia coli, while both proteins possess RNA cleavage activity, indicating that hypusination of aIF-5A is required for RNA binding but not for its RNA cleavage activity. Furthermore, we show that the hypusinated form of eIF-5A also shows RNase activity while the unmodified protein does not. Charged amino acids in the N-terminal domain of aIF-5A as well as in the C-terminal domain, which is highly similar to the cold shock protein A (CspA), an RNA chaperone of E. coli, are important for RNA cleavage activity. Moreover our results reveal that activity of aIF-5A depends on its oligomeric state. 相似文献
39.
Heine G Zucht HD Schuhmann MU Bürger K Jürgens M Zumkeller M Schneekloth CG Hampel H Schulz-Knappe P Selle H 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2002,782(1-2):353-361
Peptides, such as many hormones, cytokines and growth factors play a central role in biological processes. Furthermore, as degradation products and processed forms of larger proteins they are part of the protein turnover. Thus, they can reflect disease-related changes in an organism's homeostasis in several ways. Since two-dimensional gel electrophoresis is restricted to analysis and display of proteins with relative molecular masses above 5000, we developed Differential Peptide Display (DPD), a new technology for analysis and visualization of peptides. Here we describe its application to cerebrospinal fluid of three subjects without a disease of the central nervous system (CNS) undergoing routine myelography and of two patients suffering from a primary CNS lymphoma. Peptides with a relative molecular mass below 20000 were extracted and analysed by a combination of chromatography and mass spectrometry. The peptide pattern of a sample was depicted as a multi-dimensional peptide mass fingerprint with each peptide's position being characterized by its molecular mass and chromatographic behaviour. Such a fingerprint of a CNS sample consists of more than 6000 different signals. Data analysis of peptide patterns from patients with CNS lymphoma compared to controls revealed obvious differences regarding the peptide content of the samples. By analysing peptides within a mass range of 750-20000, DPD extends 2D gel electrophoresis, thus offering the chance to investigate CNS diseases on the level of peptides. This represents a new approach for diagnosis and possible therapy. 相似文献
40.
Dario Gastaldi Stefano Morlacchi Roberto Nichetti Claudio Capelli Gabriele Dubini Lorenza Petrini Francesco Migliavacca 《Biomechanics and modeling in mechanobiology》2010,9(5):551-561
The most common approach to treat atherosclerosis in coronary bifurcations is the provisional side-branch (PSB) stenting,
which consists sequentially of the insertion of a stent in the main branch (MB) of the bifurcation and a dilatation of the
side branch (SB) passing through the struts of the stent at the bifurcation. This approach can be followed by a redilatation
of the MB only or by a Final Kissing Balloon (FKB) inflation, both strategies leading to a minor stent distortion in the MB.
The positioning of the stent struts in the bifurcation and the stresses generated in the stent and vessel wall are worthy
of investigation for a better understanding of the mechanobiology of the system. For this purpose, a computer model of an
atherosclerotic coronary bifurcation based on the finite element method was developed; the effects of performing the final
redilatation with the two strategies utilising one or two balloons and those created by a different stent strut positioning
around the SB were investigated. Results correlate well with previous experimental tests regarding the deformation following
balloon expansion. Furthermore, results confirm firstly that the re-establishment of an optimal spatial configuration of the
stent after the PSB approach is achieved with both strategies; secondly, results show that case of stent positioning with
one cell placed centrally (with regard to the SB) should be preferred, avoiding the presence of struts inside the vessel lumen,
which may reduce hemodynamic disturbances. The central positioning also resulted in a better solution in terms of lower stresses
in the stent struts and, more importantly, in the vascular tissues. 相似文献