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61.
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Functional evaluation of domain-domain interactions and human protein interaction networks 总被引:2,自引:0,他引:2
Schlicker A Huthmacher C Ramírez F Lengauer T Albrecht M 《Bioinformatics (Oxford, England)》2007,23(7):859-865
MOTIVATION: Large amounts of protein and domain interaction data are being produced by experimental high-throughput techniques and computational approaches. To gain insight into the value of the provided data, we used our new similarity measure based on the Gene Ontology (GO) to evaluate the molecular functions and biological processes of interacting proteins or domains. The applied measure particularly addresses the frequent annotation of proteins or domains with multiple GO terms. RESULTS: Using our similarity measure, we compare predicted domain-domain and human protein-protein interactions with experimentally derived interactions. The results show that our similarity measure is of significant benefit in quality assessment and confidence ranking of domain and protein networks. We also derive useful confidence score thresholds for dividing domain interaction predictions into subsets of low and high confidence. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. 相似文献
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Gesa P?hler Cornelia Panse Ulf Diederichsen Andreas Janshoff 《Biophysical journal》2012,103(11):2295-2303
Coiled-coil formation of four different oligopeptides was characterized in solution, on hydrogels, and on membranes by employing circular dichroism spectroscopy, surface plasmon resonance spectroscopy, attenuated total reflection infrared spectroscopy, and ellipsometry. Peptide sequences rich in either glutamic acid (E: E3Cys, i-E3Cys) or lysine (K: K3Cys, i-K3Cys) were used to represent minimal mimics of eukaryotic SNARE motifs. Half of the peptides were synthesized in reverse sequence, so that parallel and antiparallel heptad coiled-coil structures were formed. Either E-peptides or K-peptides were attached covalently to phospholipid anchors via maleimide chemistry, and served as receptors for the recognition of the corresponding binding partners added to solution. Attenuated total reflection infrared spectroscopy of single bilayers confirmed the formation of coiled-coil complexes at the membrane interface. Coiled-coil formation in solution, as compared with association at the membrane surface, displays considerably larger binding constants that are largely attributed to loss of translational entropy at the interface. Finally, the fusogenicity of the various coiled-coil motifs was explored, and the results provide clear evidence that hemifusion followed by full fusion requires a parallel orientation of α-helices, whereas antiparallel oriented coiled-coil motifs display only docking. 相似文献
65.
Claudia Götz Andreas Gratz Uwe Kucklaender Joachim Jose 《Biochimica et Biophysica Acta (BBA)/General Subjects》2012,1820(7):970-977
BackgroundAbnormally high activity of protein kinase CK2 is linked to various diseases including cancer. Therefore, the inhibition of CK2 is a promising therapeutic strategy to fight this disease.MethodsWe screened a library of synthetic molecules concerning their capacity to inhibit CK2. The activity of CK2 and their IC50 and Ki values were determined by a capillary electrophoresis assay. The effects of the inhibitor in a cell culture model were analyzed by cell counting, a viability assay, cytofluorimetry and Western blot.ResultsThe best CK2 inhibitor found in this screen was 6,7-dichloro-1,4-dihydro-8-hydroxy-4-[(4-methylphenylamino)methylen]dibenzo [b,d]furan-3(2H)-one, which we refer to as “TF”. TF showed tight binding to CK2 with low IC50 (29 nM) and Ki (15 nM) values. TF inhibited only seven out of 61 human kinases tested (> 70% inhibition). Incubation of LNCaP cells with 50 μM TF for 48 h decreased the intracellular CK2 activity by 50%, confirming that the inhibitor is membrane permeable. The decrease in activity was correlated with a severe reduction in cell viability. The reduction in cell viability is at least partly due to the induction of apoptosis.General significanceIn many cancers the protein kinase CK2 is significantly up-regulated and supports the neoplastic phenotype. New therapeutic strategies should be based on diverse reliable inhibitors to reverse the abnormal high levels to normal settings. 相似文献
66.
In the dysfunctional splice variant TRPM2-ΔN, a stretch of 20 amino acids (aa 537–556) is missing within the N-terminal cytosolic
tail of the cation channel TRPM2. The ΔN-stretch overlaps with two IQ-like calmodulin-binding domains. Moreover, it contains
two PxxP motifs implicated in protein–protein interactions. Here, we constructed variants to test whether any of these motifs
may explain why TRPM2-ΔN does not respond to stimulation with either ADP ribose or hydrogen peroxide. Each of the two IQ-motifs
could be removed without loss of channel function. Similarly, deletion of either one or both PxxP motifs had no effect. Moreover,
the single point mutation D543E associated with bipolar disorder does not change the activation of TRPM2. We conclude that
no functional role can be attributed to any of the structural motifs within the ΔN-stretch that may be a spacer segment for
other functional sites in the N terminus. 相似文献
67.
Anna-Magdalena BARNISKE Thomas BORSCH Kai MLLER Michael KRUG Andreas WORBERG Christoph NEINHUIS Dietmar QUANDT 《植物分类学报》2012,50(2)
Recent phylogenetic analyses revealed a grade with Ranunculales,Sabiales,Proteales,Trochodendrales,and Buxales as first branching eudicots,with the respective positions of Proteales and Sabiales still ... 相似文献
68.
Etienne Baratchart Sébastien Benzekry Andreas Bikfalvi Thierry Colin Lindsay S. Cooley Raph?el Pineau Emeline J Ribot Olivier Saut Wilfried Souleyreau 《PLoS computational biology》2015,11(11)
The biology of the metastatic colonization process remains a poorly understood phenomenon. To improve our knowledge of its dynamics, we conducted a modelling study based on multi-modal data from an orthotopic murine experimental system of metastatic renal cell carcinoma. The standard theory of metastatic colonization usually assumes that secondary tumours, once established at a distant site, grow independently from each other and from the primary tumour. Using a mathematical model that translates this assumption into equations, we challenged this theory against our data that included: 1) dynamics of primary tumour cells in the kidney and metastatic cells in the lungs, retrieved by green fluorescent protein tracking, and 2) magnetic resonance images (MRI) informing on the number and size of macroscopic lesions. Critically, when calibrated on the growth of the primary tumour and total metastatic burden, the predicted theoretical size distributions were not in agreement with the MRI observations. Moreover, tumour expansion only based on proliferation was not able to explain the volume increase of the metastatic lesions. These findings strongly suggested rejection of the standard theory, demonstrating that the time development of the size distribution of metastases could not be explained by independent growth of metastatic foci. This led us to investigate the effect of spatial interactions between merging metastatic tumours on the dynamics of the global metastatic burden. We derived a mathematical model of spatial tumour growth, confronted it with experimental data of single metastatic tumour growth, and used it to provide insights on the dynamics of multiple tumours growing in close vicinity. Together, our results have implications for theories of the metastatic process and suggest that global dynamics of metastasis development is dependent on spatial interactions between metastatic lesions. 相似文献
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