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991.
Suzanne de Treville Samuel Bendahan Annelies Vanderhaeghe 《Flexible Services and Manufacturing Journal》2007,19(4):334-357
How firms scan and interpret their environments has implications for the flexibility strategy that they choose, as well as for the performance of that strategy. We extend Daft and Weick’s (Acad Manage Rev 9(2):284–295, 1984) model of firms as interpretation systems into a theoretical model of flexibility performance through extended iterations between observations of a failed flexibility initiative and relevant literature. We test the model using well-known teaching cases. We argue that the use of an iterative process that involves cases and theory both stimulates creativity in integrating theory and lays an initial foundation for evidence-based practice. 相似文献
992.
Ewald AH Fritschi G Maurer HH 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2007,857(1):170-174
The amphetamine-derived designer drug 4-iodo-2,5-dimethoxy-amphetamine (DOI) is an upcoming substance on the illicit drug market. In the current study, the identification of its metabolites in rat urine and their toxicological detection in the authors' systematic toxicological analysis (STA) procedure were examined. DOI is extensively metabolized by O-demethylation and beside small amounts of parent compound it was found to be excreted mainly in form of metabolites. The STA procedure using full-scan GC-MS allowed proving an intake of a common drug users' dose of DOI by detection of the two O-demethyl metabolite isomers in rat urine. Assuming similar metabolism, the described STA procedure should be suitable for proof of an intake of DOI in human urine. 相似文献
993.
Abstact Polar organisms should have mechanisms to survive the extremely cold environment. Four genes encoding cold-shock proteins,
which are small, cold-induced bacterial proteins, have been cloned from the Antarctic bacterium Streptomyces sp. AA8321. Since the specific functions of any polar bacterial or Streptomyces cold-shock proteins have not yet been determined, we examined the role of cold-shock protein A from Streptomyces sp. AA8321 (CspASt). Gel filtration chromatography showed that purified CspASt exists as a homodimer under physiological conditions, and gel shift assays showed that it binds to single-stranded, but not
double-stranded, DNA. Overexpression of CspASt in Escherichia coli severely impaired the ability of the host cells to form colonies, and the cells developed an elongated morphology. Incorporation
of a deoxynucleoside analogue, 5-bromo-2′-deoxyuridine, into newly synthesized DNA was also drastically diminished in CspASt-overexpressing cells. These results suggest that CspASt play a role in inhibition of DNA replication during cold-adaptation. 相似文献
994.
The GrpE protein from E. coli is a homodimer with an unusual structure of two long paired α-helices from each monomer interacting in a parallel arrangement
to form a “tail” at the N-terminal end. Using site-directed mutagenesis, we show that there is a key electrostatic interaction
involving R57 (mediated by a water molecule) that provides thermal stability to this “tail” region. The R57A mutant showed
a drop in T
m of 8.5°C and a smaller ΔH
u (unfolding) compared to wild-type for the first unfolding transition, but no significant decrease in dimer stability as shown
through equilibrium analytical ultracentrifugation studies. Another mutant (E94A) at the dimer interface showed a decrease
in ΔH
u but no drop in T
m for the second unfolding transition and a slight increase in dimer stability. 相似文献
995.
The issue of amino acid depth in proteins gives important insights to our understanding of protein’s three-dimensional structure.
There has already been much research done in mathematical and statistical sciences regarding the general definitions, properties
and algorithms describing the particle depth of spatially extended systems. We constructed a method of calculating the amino
acids depths and applied it to a set of 527 protein structures. We propose the introduction of amino acid depth tendency factors
for three-dimensional structures of proteins. The depth tendency factors relate not only to the hydrophobicity indices but
also to the electrostatic charge. We found a relationship between the protein size and the number of residues using the distance
between the deepest residue and surface residues. We made a prediction regarding the number of residues on the surface of
a protein, the deepest amino acid, and the average depth, all of which are fitted well to a linear functional relationship
with the length of the protein. Finally, we have predicted the depths of multiple peptides in protein’s three-dimension structure.
Electronic supplementary material The online version of this article () contains supplementary material, which is available to authorized users. 相似文献
996.
Typical physico-chemical studies of metal binding proteins are usually aimed at determination of the metal binding constant
K for a native protein (K
n), while the significance of the K value for the thermally denatured protein (K
u) is usually underestimated. Meanwhile, metal binding induced shift of thermal denaturation transition of a single site metal
binding protein is defined by K
n to K
u ratio, implying that knowledge of both K values is required for full characterization of the system. In the present work, the most universal approach to the studies
of single site metal binding proteins, namely construction of a protein “phase diagram” in coordinates of free metal ion concentration
– temperature, is considered in detail. The detailed algorithm of construction of the phase diagrams along with underlying
mathematic procedures developed here may be of use for studies of other simple protein-target type systems, where target represents
low molecular weight ligand. Analysis of the simplest protein-ligand system reveals that thermodynamic properties of apo-protein
dictate the maximal possible increase of its affinity to any simple ligand upon thermal denaturation of the protein. Experimental
and general problems coupled with the use of the phase diagrams are discussed. 相似文献
997.
The polypeptides integrating amaranth globulin-p and 11S-globulin were characterized by two-dimensional electrophoresis, ion-exchange
chromatography and RP-HPLC. All polypeptides exhibited charge and hydrophobic heterogeneity. Almost all acid (A, pI 5–7) and
basic (B, pI 9–10) polypeptides were present in both globulins, and the same happened with the unprocessed M polypeptides
with pI in the range of 7–7.5 which fits well with a sequence containing both the A and B polypeptides. There were other polypeptides
only present in 11S-globulin, like some of 41 and 16 kDa, which might come from another precursor or be the products of a
different processing of the propolypeptide. These results suggested that, although amaranth subunits from different subfamilies
are interchangeable in different oligomers, some structural differences between them might affect the assembly of globulin
molecules. Structural differences arising from this behavior could account for the different physicochemical properties of
globulin molecules. 相似文献
998.
Srinivasulu S Acharya AS Prabhakaran M Fabry ME Alami R Fiering SN Bouhasirra EE Nagel RL 《The protein journal》2007,26(8):523-532
Recombinant α-Savaria globin (αS49R) was assembled with βS chains by the alloplex intermediate pathway to generate tetrameric rHbS-Sarvaria (α2S49Rβ2E6V) that exhibited normal O2 affinity and co-operatively at pH 7.4. Allosteric effectors, 2,3-DPG, L35, and NaCl increased O2 affinity by 15%. Bohr effects were similar for rHbS-Savaria and HbS (0.38 ± 0.025 vs. 0.46 ± 0.03, respectively). The CSAT of HbS increased from 16.7 ± 0.8 to 27.0 ± 1.0 g/dL. Co-polymerization demonstrated inhibition predominantly by the Cis-dimer.
Molecular modeling indicated that the positive charge at α-49 generated a strong anion-binding site and reduced flexibility
of the CD-region by restricting movement in the E and F helices. The molecular distance between Arg-49 and Asn-78 in the neighboring
double strand decreased, and electrostatic repulsion between the inter-double strands increased, resulting in inhibition of
polymerization. The Savaria mutation may be useful for the design of super-inhibitory α-chains and gene therapy of sickle
cell anemia. 相似文献
999.
A mixture of 4-chloro-1-butanol and 2,2,2-Trifluoroethanol (TFE) has been used to generate Molten globule (MG) state of structurally
homologous but functionally different proteins bovine α-lactalbumin and hen egg-white lysozyme. The thermal denaturation was
done using UV–Visible spectroscopy. From UV–Visible profile, thermal transition was not observed beyond a particular concentration.
There was an indication of molten globule state in case of α-lactalbumin from circular dichroism experiments. By intrinsic
tryptophan fluorescence, acrylamide and potassium iodide quenching, 8-anilino-naphthalene sulfonic acid (ANS) binding and
energy transfer studies the presence of molten globule state was confirmed. Quantitative characterization of MG state and
determining the binding thermodynamics of ANS to the MG state was done using Isothermal Titration Calorimetry (ITC). Results
show that α-lactalbumin exists in MG state at a particular concentration but lysozyme does not show features of MG state. 相似文献
1000.
3D-QSAR studies of Dipeptidyl peptidase IV inhibitors using a docking based alignment 总被引:1,自引:0,他引:1
Dipeptidyl peptidase IV (DPP-IV) deactivates the incretin hormones GLP-1 and GIP by cleaving the penultimate proline or alanine
from the N-terminal (P1-position) of the peptide. Inhibition of this enzyme will prevent the degradation of the incretin hormones
and maintain glucose homeostasis; this makes it an attractive target for the development of drugs for diabetes. This paper
reports 3D-QSAR analysis of several DPP-IV inhibitors, which were aligned by the receptor-based technique. The conformation
of the molecules in the active site was obtained through docking methods. The QSAR models were generated on two training sets
composed of 74 and 25 molecules which included phenylalanine, thiazolidine, and fluorinated pyrrolidine analogs. The 3D-QSAR
models are robust with statistically significant r2, q2, and values. The CoMFA and CoMSIA models were used to design some new inhibitors with several fold higher binding affinity.
Figure The CoMFA contours around molecule D1T155 (a) steric contours - favored (green); disfavored (yellow) (b) electrostatic contours
- electropositive (blue); electronegative (red) 相似文献