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51.
Identification of Compounds that Selectively Stabilize Specific G‐Quadruplex Structures by Using a Thioflavin T‐Displacement Assay as a Tool 下载免费PDF全文
Dr. Jan Jamroskovic Dr. Madeleine Livendahl Dr. Jonas Eriksson Dr. Erik Chorell Dr. Nasim Sabouri 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(52):18932-18943
Small molecules are used in the G‐quadruplex (G4) research field in vivo and in vitro, and there are increasing demands for ligands that selectively stabilize different G4 structures. Thioflavin T (ThT) emits an enhanced fluorescence signal when binding to G4 structures. Herein, we show that ThT can be competitively displaced by the binding of small molecules to G4 structures and develop a ThT‐displacement high‐throughput screening assay to find novel and selective G4‐binding compounds. We screened approximately 28 000 compounds by using three different G4 structures and identified eight novel G4 binders. Analysis of the structural conformation and stability of the G4 structures in presence of these compounds demonstrated that the four compounds enhance the thermal stabilization of the structures without affecting their structural conformation. In addition, all four compounds also increased the G4‐structure block of DNA synthesis by Taq DNA polymerase. Also, two of these compounds showed selectivity between certain Schizosaccharomyces pombe G4 structures, thus suggesting that these compounds or their analogues can be used as selective tools for G4 DNA studies. 相似文献
52.
Michelle Co Camilla Zettersten Leif Nyholm Per J.R. Sjöberg Charlotta Turner 《Analytica chimica acta》2012
Experiments with birch bark samples have been carried to enable a distinction between extraction and degradation effects during pressurised hot water extraction. Two samples, E80 and E180, contained birch bark extracts obtained after extraction at 80 and 180 °C for up to 45 min, respectively. Two other samples, P80 and P180, were only extracted for 5 min at the two temperatures and were thereafter filtered and hydrothermally treated at 80 and 180 °C, respectively. During the latter treatment, samples were collected at different times to assess the stability of the extracted compounds. An offline DPPH (2,2-diphenyl-1-picrylhydrazyl) assay, as well as a high performance liquid chromatographic separation coupled to an electrochemical detector, were used to determine the antioxidant capacity of the processed samples. The results obtained with the different techniques were compared to assess the yield of the extraction and degradation processes. In addition, an online hyphenated system comprising high performance liquid chromatography coupled to diode-array; electrochemical; and tandem mass spectrometric detection (HPLC-DAD-ECD-MS/MS) was used to study the compositions of the extracts in more detail. The results for the samples processed at 80 °C showed that the extraction reached a steady-state already after 5 min, and that the extracted compounds were stable throughout the entire extraction process. Processing at 180 °C, on the other hand, gave rise to partly degraded extracts with a multitude of peaks in both the diode array and electrochemical detectors, and a higher antioxidant capacity compared to for the extracts obtained at 80 °C. It is concluded that HPLC-DAD-ECD is a more appropriate technique for the determination of antioxidants than the DPPH assay. The mass spectrometric results indicate that one of the extracted antioxidants, catechin, was isomerised to its diastereoisomers; (+)-catechin, (−)-catechin, (+)-epicatechin, and (−)-epicatechin. 相似文献
53.
54.
Leif Holmlid 《Journal of nanoparticle research》2010,12(1):273-284
Recently, rotational spectroscopy in the radio frequency range was used to determine the bond lengths in several types of
potassium Rydberg Matter (RM) clusters with high precision (Mol Phy 105: 933–939, 2007). Due to the large bond lengths of
a few nm and well-ordered structure of such clusters, it is expected that light scattering can be used to determine their
dimensions. A weak carbon dioxide laser beam is introduced collinearly into a tunable RM cavity. When RM is formed, a very
pronounced fringe structure with several hundred fringes is observed at the detector as a function of the grating position.
These fringes show a phase delay of the carbon dioxide laser light caused by reflections within the RM clusters. The delay
lengths derived from the fringe structure give distances between the rows of atoms in the clusters. The excitation level of
the most easily observed clusters is n = 5. Clusters with n = 6, 7, and 8 are also commonly detected. The bond distance for n = 5 is found to be 3.804 ± 0.015 nm, while that for n = 6 is 5.525 ± 0.014 nm, in accurate agreement with values from rotational spectroscopy. 相似文献
55.
Theoretical prediction of the protein–protein interaction between Arabidopsis thaliana COP1 and UVR8
In plants, ultraviolet-B radiation (280–315 nm) regulates gene expression and plant morphology through the UV RESPONSE LOCUS 8 (UVR8) photoreceptor. The first signaling event after quantal absorbance is the interaction of the UVR8 C-terminus with the E3 ubiquitin ligase CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1). The nature of the interaction between these two proteins is hitherto unknown. A protein homology model of the Arabidopsis thaliana COP1 seven-bladed propeller WD40 repeat domain and de novo folds of the C-terminal 27 amino acid (amino acids 397–423) peptide of Arabidopsis UVR8 (UVR8397?423) is herein reported. Using a theoretical computational docking protocol, the interaction between COP1 and UVR8 was predicted. A core motif was identified in UVR8397?423 comprising adjacent hydrophobic residues V410 and P411 together with a charged residue D412, homologous to corresponding motifs in other COP1-binding proteins, such as ELONGATED HYPOCOTYL 5 (HY5), cryptochrome 1 (CRY1), and salt tolerance proteins STO/STH. The protein–protein interaction between the COP1 WD40 repeat domain and UVR8397?423 reveals binding within a region of COP1 overlapping with the binding site for HY5 and the other COP1-interacting proteins. This study provides a framework for understanding docking between UVR8 and COP1, which in turn gives clues for experimental testing of UVR8/COP1 interaction. 相似文献
56.
Jonas Örtegren Philippe Busson Ulf W. Gedde Anders Hult Anders Eriksson Mikael Lindgren 《Liquid crystals》2013,40(6):861-868
We report second harmonic generation in a ferroelectric liquid crystalline trimer and ferroelectric liquid crystalline dendrimers of first, second and third generation. Thin cells were filled with the compounds by capillary forces at elevated temperature, and cooled from the surface stabilized ferroelectric state to below the glass transition temperature, while kept in an electric field. The cone motion viscosity and the threshold electric field for unwinding of the helix axis of the chiral tilted smectic mesophases were studied separately at elevated temperature, and these data were used to optimize the preparation of the films. The measured response time was between 0.3 and 3ms, which corresponds to a cone motion viscosity between 0.5 and 50 Pa s. Second harmonic generation was studied both at elevated temperature with an electric field and at room temperature with and without electric field. The first generation dendrimer exhibited a strong increase in the second order non-linear optical response with time at room temperature. The d 23-coefficient of this dendrimer was approximately four times larger than for the other macromolecules and was 0.045 pm V-1. The relatively large d-coefficient of the first generation dendrimer is ascribed to crystallization, which improved the orientation of the molecular dipoles. 相似文献
57.
Dr. Ramasamy Jayarajan Tautvydas Kireilis Prof. Lars Eriksson Prof. Kálmán J. Szabó 《Chemistry (Weinheim an der Bergstrasse, Germany)》2022,28(58):e202202059
A broad range of aliphatic, aromatic, and heterocyclic boronic acids were successfully homologated using trifluorodiazoethane in the presence of BINOL derivatives to provide the corresponding chiral trifluoromethyl containing boronic acid derivatives in high yields and excellent enantioselectivity. The in situ conversion of the chiral transient boronic acids to the corresponding alcohols or β-CF3 carboxylates are also demonstrated. 相似文献
58.
Kristina Westerlund Anders Myrhammar Hanna Tano Maxime Gestin Amelie Eriksson Karlstrm 《Molecules (Basel, Switzerland)》2021,26(10)
Natural backbone-cyclized proteins have an increased thermostability and resistance towards proteases, characteristics that have sparked interest in head-to-tail cyclization as a method to stability-enhance proteins used in diagnostics and therapeutic applications, for example. In this proof-of principle study, we have produced and investigated a head-to-tail cyclized and HER2-specific ZHER2:342 Affibody dimer. The sortase A-mediated cyclization reaction is highly efficient (>95%) under optimized conditions, and renders a cyclic ZHER3:342-dimer with an apparent melting temperature, Tm, of 68 °C, which is 3 °C higher than that of its linear counterpart. Circular dichroism spectra of the linear and cyclic dimers looked very similar in the far-UV range, both before and after thermal unfolding to 90 °C, which suggests that cyclization does not negatively impact the helicity or folding of the cyclic protein. The cyclic dimer had an apparent sub-nanomolar affinity (Kd ~750 pM) to the HER2-receptor, which is a ~150-fold reduction in affinity relative to the linear dimer (Kd ~5 pM), but the anti-HER2 Affibody dimer remained a high-affinity binder even after cyclization. No apparent difference in proteolytic stability was detected in an endopeptidase degradation assay for the cyclic and linear dimers. In contrast, in an exopeptidase degradation assay, the linear dimer was shown to be completely degraded after 5 min, while the cyclic dimer showed no detectable degradation even after 60 min. We further demonstrate that a site-specifically DyLight 594-labeled cyclic dimer shows specific binding to HER2-overexpressing cells. Taken together, the results presented here demonstrate that head-to-tail cyclization can be an effective strategy to increase the stability of an Affibody dimer. 相似文献
59.
Cell Tracking with Caged Xenon: Using Cryptophanes as MRI Reporters upon Cellular Internalization 下载免费PDF全文
Stefan Klippel Jörg Döpfert Dr. Jabadurai Jayapaul Martin Kunth Federica Rossella Matthias Schnurr Dr. Christopher Witte Dr. Christian Freund Dr. Leif Schröder 《Angewandte Chemie (International ed. in English)》2014,53(2):493-496
Caged xenon has great potential in overcoming sensitivity limitations for solution‐state NMR detection of dilute molecules. However, no application of such a system as a magnetic resonance imaging (MRI) contrast agent has yet been performed with live cells. We demonstrate MRI localization of cells labeled with caged xenon in a packed‐bed bioreactor working under perfusion with hyperpolarized‐xenon‐saturated medium. Xenon hosts enable NMR/MRI experiments with switchable contrast and selectivity for cell‐associated versus unbound cages. We present MR images with 103‐fold sensitivity enhancement for cell‐internalized, dual‐mode (fluorescence/MRI) xenon hosts at low micromolar concentrations. Our results illustrate the capability of functionalized xenon to act as a highly sensitive cell tracer for MRI detection even without signal averaging. The method will bridge the challenging gap for translation to in vivo studies for the optimization of targeted biosensors and their multiplexing applications. 相似文献
60.
Back Cover: Cell Tracking with Caged Xenon: Using Cryptophanes as MRI Reporters upon Cellular Internalization (Angew. Chem. Int. Ed. 2/2014) 下载免费PDF全文