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121.
Woo Seung Son Kyu-Sung Jeong Sang Min Lim Ae Nim Pae 《Bioorganic & medicinal chemistry letters》2019,29(10):1168-1172
Highly effective and safe drugs for the treatment of neuropathic pain are urgently required and it was shown that blocking T-type calcium channels can be a promising strategy for drug development for neuropathic pain. We have developed pyrrolidine-based T-type calcium channel inhibitors by structural hybridization and subsequent assessment of in vitro activities against Cav3.1 and Cav3.2 channels. Profiling of in vitro ADME properties of compounds was also carried out. The representative compound 17h showed comparable in vivo efficacy to gabapentin in the SNL model, which indicates T-type calcium channel inhibitors can be developed as effective therapeutics for neuropathic pain. 相似文献
122.
Megan L. Machek Halie A. Sonnenschein Sasha‐Kaye I. Graham Flowreen Shikwana Seung‐Hwan L. Kim Selena Garcia DuBar Ian D. Minzer Ryan Wey Jessica K. Bell 《Protein science : a publication of the Protein Society》2019,28(8):1423-1436
Suppressor of IKKepsilon (SIKE) is a 207 residue protein that is implicated in the TLR3‐TANK‐binding kinase‐1‐mediated response to viral infection. SIKE's function in this pathway is unknown, but SIKE forms interactions with two distinct cytoskeletal proteins, α‐actinin and tubulin, and SIKE knockout reduces cell migration. As structure informs function and in the absence of solved structural homologs, our studies were directed toward creating a structural model of SIKE through biochemical and biophysical characterization to probe and interrogate SIKE function. Circular dichroism revealed a primarily (73%) helical structure of minimal stability (<Tm > =32°C) but reversibly denatured. Limited proteolysis (LP) and chemical modification identified the N‐terminal 2/3 of the protein as dynamic and accessible, whereas size exclusion chromatography (SEC) confirmed three homo‐oligomeric species. SEC coupled to chemical crosslinking characterized the primary species as dimeric, a secondary hexameric species, and a higher order aggregate/polymer. Fluorescence polarization using intrinsic tryptophan fluorescence contextualized the anisotropy value for the SIKE dimer (molecular weight 51.8 kDa) among proteins of known structure, bovine serum albumin (BSA; 66 kDa), and glutamate dehydrogenase (GDH; 332 kDa). Radii of gyration for BSA and GDH provided exclusionary values for SIKE tertiary and dimeric quaternary models that otherwise conformed to secondary structure, LP, and modification data. Dimeric quaternary models were further culled using acrylamide quenching data of SIKE's single tryptophan that showed a single, protected environment. The low cooperativity of folding and regions of dynamic and potentially disordered structure advance the hypothesis that SIKE forms a conformational ensemble of native states that accommodate SIKE's interactions with multiple, distinct protein‐binding partners. 相似文献
123.
124.
Cui Heqing Song Myoung Chong Lee Ji Young Yoon Yeo Joon 《Journal of industrial microbiology & biotechnology》2019,46(12):1707-1713
Journal of Industrial Microbiology & Biotechnology - Methylated flavonoids possess improved bioactivities compared to their unmethylated counterparts. In this study, for the efficient... 相似文献
125.
Iyll‐Joon Doh Jennifer Sturgis Diana V. Sarria Zuniga Robert E. Pruitt J. Paul Robinson Euiwon Bae 《Journal of biophotonics》2019,12(12)
The forward elastic‐light‐scattering pattern of a bacterial colony reflects its morphological characteristics. Three bacteria genera whose colonies having convex, crateriform, or irregular elevation were investigated to study the correlation between the morphology and the scattering pattern of the colony. The difference in the colony elevation produced distinct shapes of light diffraction in the scattering pattern, resulting circular diffraction rings or scattered light. Further details can be found in the article by Iyll‐Joon Doh, Jennifer Sturgis, Diana V. Sarria Zuniga, et al. ( e201900149 ).
126.
Active hemostatic agents can play a crucial role in saving patients’ lives during surgery. Active hemostats have several advantages including utilization of natural blood coagulation and biocompatibility. Among them, although human neutrophil peptide‐1 (HNP‐1) has been previously reported with the hemostatic mechanism, which part of HNP‐1 facilitates the hemostatic activity is not known. Here, a partial peptide (HNP‐F) promoting hemostasis, originating from HNP‐1, has been newly identified by the blood coagulation ability test. HNP‐F shows the best hemostatic effect between the anterior half and posterior half of peptides. Moreover, microscopic images show platelet aggregation and an increase in the concentration of platelet factor 4, and the scanning electron microscope image of platelets support platelet activation by HNP‐F. Thromboelastography indicates decreased clotting time and increased physical properties of blood clotting. Mouse liver experiments demonstrate improved hemostatic effect by treatment of peptide solution. Cell viability and hemolysis assays confirm the HNP‐F's biosafety. It is hypothesized that the surface charge and structure of HNP‐F could be favorable to interact with fibrinogen or thrombospondin‐1. Collectively, because HNP‐F as an active peptide hemostat has many advantages, it could be expected to become a potent hemostatic biomaterial, additive or pharmaceutical candidate for various hemostatic applications. 相似文献
127.
XNP/ATRX, a causative gene of X-linked alpha-thalassemia/mental retardation syndrome, encodes an SNF2 family ATPase/helicase protein. To better understand the role of XNP/ATRX in development, we isolated and characterized a Drosophila XNP/ATRX homolog, dXNP, which contains highly conserved SNF2 and helicase domains. Ectopically expressed dXNP induced strong apoptosis in the developing eye and wing, but did not affect cell cycle progression or the expression of wingless and engrailed, essential regulators of development. The dXNP-induced apoptosis was strongly suppressed by DJNKK/hemipterous mutation, and dXNP increased JNK activity. Taken together, these results suggest that dXNP regulates apoptosis via JNK activation. 相似文献
128.
Hwang J Kalinin A Hwang M Anderson DE Kim MJ Stojadinovic O Tomic-Canic M Lee SH Morasso MI 《The Journal of biological chemistry》2007,282(25):18645-18653
The novel Ca2+-binding protein, Scarf (skin calmodulin-related factor) belongs to the calmodulin-like protein family and is expressed in the differentiated layers of the epidermis. To determine the roles of Scarf during stratification, we set out to identify the binding target proteins by affinity chromatography and subsequent analysis by mass spectrometry. Several binding factors, including 14-3-3s, annexins, calreticulin, ERp72 (endoplasmic reticulum protein 72), and nucleolin, were identified, and their interactions with Scarf were corroborated by co-immunoprecipitation and co-localization analyses. To further understand the functions of Scarf in epidermis in vivo, we altered the epidermal Ca2+ gradient by acute barrier disruption. The change in the expression levels of Scarf and its binding target proteins were determined by immunohistochemistry and Western blot analysis. The expression of Scarf, annexins, calreticulin, and ERp72 were up-regulated by Ca2+ gradient disruption, whereas the expression of 14-3-3s and nucleolin was reduced. Because annexins, calreticulin, and ERp72 have been implicated in Ca2+-induced cellular trafficking, including the secretion of lamellar bodies and Ca2+ homeostasis, we propose that the interaction of Scarf with these proteins might be crucial in the process of barrier restoration. On the other hand, down-regulation of 14-3-3s and nucleolin is potentially involved in the process of keratinocyte differentiation and growth inhibition. The calcium-dependent localization and up-regulation of Scarf and its binding target proteins were studied in mouse keratinocytes treated with ionomycin and during the wound-healing process. We found increased expression and nuclear presence of Scarf in the epidermis of the wound edge 4 and 7 days post-wounding, entailing the role of Scarf in barrier restoration. Our results suggest that Scarf plays a critical role as a Ca2+ sensor, potentially regulating the function of its binding target proteins in a Ca2+-dependent manner in the process of restoration of epidermal Ca2+ gradient as well as during epidermal barrier formation. 相似文献
129.
Pyrolysis mass spectrometry (PyMS) is a rapid, simple, high-resolution analytical method based on thermal degradation of complex
material in a vacuum, and has been widely applied to the discrimination of closely related microbial strains. Minimally prepared
samples of embryogenic and non-embryogenic calluses derived from various higher plants (sweet potato, morning glory, Korean
ginseng, Siberian ginseng, and balloon flower) were subjected to PyMS for spectral fingerprinting. A dendrogram based on the
unweighted pair group method, with arithmetic mean of pyrolysis mass spectra, divided the calluses into Siberian ginseng embryogenic
callus and the others, which were subsequently divided into embryogenic and non-embryogenic callus groups, regardless of plant
species from which the calluses were derived. In the non-embryogenic callus group, the dendrogram was in agreement with the
known taxonomy of the plants. These results indicate that PyMS analysis could be applied for discriminating plant calluses
based on embryogenic capacity and taxonomic classification. 相似文献
130.
Microsomal prostaglandin E2 synthase (mPGES-1) has been identified recently as a novel target for treating pain and inflammation. The aim of this study
is to understand the binding affinities of reported inhibitors for mPGES-1 and further to design potential new mPGES-1 inhibitors.
3D-QSAR-CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity indices analysis) - techniques
were employed on a series of indole derivatives that act as selective mPGES-1 inhibitors. The lowest energy conformer of the
most active compound obtained from systematic conformational search was used as a template for the alignment of 32 compounds.
The models obtained were used to predict the activities of the test set of eight compounds, and the predicted values were
in good agreement with the experimental results. The 3D-QSAR models derived from the training set of 24 compounds were all
statistically significant (CoMFA; q
2 = 0.89, r
2 = 0.95, , and CoMSIA; q
2 = 0.84, r
2 = 0.93, , ). Contour plots generated for the CoMFA and CoMSIA models reveal useful clues for improving the activity of mPGES-1 inhibitors.
In particular, substitutions of an electronegative fluorine atom or a bulky hydrophilic phenoxy group at the meta or para positions of the biphenyl rings might improve inhibitory activity. A plausible binding mode between the ligands and mPGES-1
is also proposed. 相似文献