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101.
Haque A Rai V Bahal BS Shukla S Lattif AA Mukhopadhyay G Prasad R 《Biochemical and biophysical research communications》2007,352(2):491-497
Candida drug resistance protein (Cdr1p) is a major drug efflux protein, which plays a key role in commonly encountered clinical azole resistance in Candida albicans. We have analyzed its sequence in several azole resistant clinical isolates to evaluate the allelic variation within CDR1 gene and to relate it to its functional activity. The sequence analysis revealed 53 single nucleotide polymorphisms (SNPs), out of which six were non-synonymous single nucleotide polymorphisms (NS-SNPs) implying a change in amino acid and were found in two or more than two allelic combinations in different sensitive or resistant isolates. We have identified three new NS-SNPs namely, E948P, T950S, and F1399Y, in isolates wherein F1399Y appeared to be unique and was present in one of the naturally occurring azole resistant isolates obtained from Indian diabetic patients. However, site-directed mutagenesis showed that the residue F1399 in between TMS 11 and TMS 12 does not affect the functionality of Cdr1p. Taken together, our SNPs analyses reveal that unlike human P-gp, the naturally acquired allelic variations are mostly present in non-conserved regions of the protein which do not allow Cdr1p to genetically evolve in a manner, that would allow a change in its functionality to affect substrate recognition, specificity, and drug efflux activity of C. albicans cells. 相似文献
102.
103.
Chitra Sudarshan Linda Yaswen Ashok Kulkarni Rajendra Raghow 《Journal of cellular physiology》1998,176(1):67-75
The profound effects of transforming growth factor β1 (TGF-β1) on the immune system, cardiogenesis, in yolk sac hematopoeisis and in differentiation of endothelium have been demonstrated by detailed analyses of TGF-β1 knockout mice during embryogenesis. We have systematically examined the autocrine and paracrine roles of TGF-β1 in cell proliferation and in its ability to modulate the gene expression of selected components of extracellular matrix (ECM) using embryonic fibroblasts from TGF-β1 null mice (TGF-β1−/−). The rates of cell proliferation of embryonic fibroblasts from normal mice (TGF-β1+/+) and TGF-β1 null mice were compared by cell counting, by 3H thymidine incorporation, and by measuring the fraction of cells in the G1, S, and G2/M phases of the cell cycle by fluorescent activated cell sorting (FACS). Concurrently, the expression of pro-α1(I) collagen, fibronectin, and plasminogen activator inhibitor-1 (PAI-1) was also quantified by hybridization of total mRNA from TGF-β1+/+ and TGF-β1−/− embryonic fibroblasts. We report that TGF-β1−/− cells proliferated at about twice the rate of TGF-β1+/+ cells. Further, TGF-β1 null fibroblasts accumulated and synthesized lower constitutive levels of pro-α1(I) collagen, fibronectin, and PAI-1 mRNA. The quantitative differences in the rates of cell proliferation and ECM gene expression between TGF-β1+/+ and TGF-β1−/− cells could be eliminated by treatment of TGF-β1+/+ cells with a neutralizing antibody of TGF-β1. Thus, our results are consistent with the hypothesis that TGF-β1 acts as a negative autocrine regulator of growth and a positive autocrine regulator of ECM biosynthesis in embryonic fibroblasts. 176:67–75, 1998. Published 1998 Wiley-Liss, Inc. 1 This article was prepared by a group of United States government employees and non-United States government employees, and as such is subject to 17 U.S.C. Sec. 105. 相似文献
104.
Parab Ankita Rajendra Lynn Chew Bee Subramaniam Sreeramanan 《Molecular biology reports》2021,48(11):7223-7231
Molecular Biology Reports - Clonal propagation is one of the attributes of plant tissue culture. Therefore, analysis of genetic stability among the in vitro cultured plants is a crucial step. It... 相似文献
105.
Rajendra Varma Ranbir S. Varma Williams S. Allen Ahmad H. Wardi 《Biochimica et Biophysica Acta (BBA)/General Subjects》1974,362(3):584-588
Fractional molar ratios of serine, threonine and aspartic acid to neutral sugars in the purified bovine vitreous humor hyaluronate, and a 4–5-fold increase in the percentage of these amino acids and the absence of sugar alditols in hyaluronate reduced with NaBH4---PdCl2 after alkali treatment indicated the absence of a carbohydrate—protein linkage. Gel filtration behavior, a decrease in intrinsic viscosity of reduced hyaluronate to about one-half and a significant decrease in its specific rotation suggested that the two antiparallel chains of the hyaluronate double helix may come apart upo reduction. The vitreous humor hyaluronate contained 109.2 ppm of “bound” silicon. It is suggested that the bound silicon may bridge the two antiparallel chains through the neutral sugars and/or through the hydroxyl group of the uronic acid moiety. 相似文献
106.
Grossman PM Linares OA Supiano MA Oral H Mehta RH Starling MR 《American journal of physiology. Heart and circulatory physiology》2004,287(2):H878-H888
Objectives of this study were to develop a technique for quantifying cardiac-specific norepinephrine (NE) mass transport and determine whether cardiac NE kinetic modeling parameters were related to physiological variables of left ventricular (LV) size and systolic performance in nine patients with chronic mitral regurgitation. Biplane contrast cineventriculograms were used to determine LV size and ejection fraction (EF), micromanometer LV pressures and radionuclide LV volumes from a range of loading conditions to calculate LV end-systolic elastance, and [(3)H]NE infusions with LV and coronary sinus sampling for [(3)H]NE and endogenous NE during and after termination of infusions to model NE mass transport. Total NE release rate into cardiac interstitial fluid (M(IF)(R)) averaged 859 +/- 214 and NE released de novo into cardiac interstitial fluid (M(IF)(u,r,en)) averaged 546 +/- 174 pmol/min. Both M(IF)(R) and M(IF)(u,r,en)correlated directly with LV end-systolic volume (r = 0.84, P = 0.005; r = 0.86, P = 0.003); inversely with LV EFs (r = -0.75, P = 0.02; r = -0.81, P = 0.008); and inversely with LV end-systolic elastance values, optimally fit by a nonlinear function (r = 0.89, P = 0.04; r = 0.96, P = 0.01). We conclude that total and newly released NE into interstitial fluid of the heart, determined by regional mass transport kinetic model, are specific measures of regional cardiac-specific sympathetic nervous system activity and are strongly related to measures of LV size and systolic performance. These data support the concept that this new model of organ-specific NE kinetics has physiological relevance. 相似文献
107.
Ashwini Jadhav Bhagyashree Bansode Datta Phule Amruta Shelar Rajendra Patil Wasudev Gade Kiran Kharat Sankunny Mohan Karuppayil 《World journal of microbiology & biotechnology》2017,33(5):96
Fluoroquinolines are broad spectrum fourth generation antibiotics. Some of the Fluoroquinolines exhibit antifungal activity. We are reporting the potential mechanism of action of a fluoroquinoline antibiotic, moxifloxacin on the growth, morphogenesis and biofilm formation of the human pathogen Candida albicans. Moxifloxacin was found to be Candidacidal in nature. Moxifloxacin seems to inhibit the yeast to Hyphal morphogenesis by affecting signaling pathways. It arrested the cell cycle of C. albicans at S phase. Docking of moxifloxacin with predicted structure of C. albicans DNA Topoisomerase II suggests that moxifloxacin may bind and inhibit the activity of DNA Topoisomerase II in C. albicans. Moxifloxacin could be used as a dual purpose antibiotic for treating mixed infections caused by bacteria as well as C. albicans. In addition chances of developing moxifloxacin resistance in C. albicans are less considering the fact that moxifloxacin may target multiple steps in yeast to hyphal transition in C. albicans. 相似文献
108.
Wansi JD Wandji J Kamdem Waffo AF Ngeufa HE Ndom JC Fotso S Maskey RP Njamen D Fomum TZ Laatsch H 《Phytochemistry》2006,67(5):475-480
Two alkaloid derivatives, oriciacridone A and B, were isolated from the stem bark of Oriciopsis glaberrima (Rutaceae). The structures were elucidated by a detailed spectroscopic analysis. The extract exhibited in vitro significant antimicrobial activity against a range of micro-organisms. 相似文献
109.
Rajendra G. Mehta Leonard J. Schiff Steven J. Moore Ann Marie Buckley Marcia I. Dawson 《In vitro cellular & developmental biology. Plant》1986,22(3):164-168
Summary The mechanism of action of retinoid in reversing keratinization in hamster trachea is yet unknown. The purpose of this study
was to determine if cellular retinoic acid binding protein (CRABP) is present in tracheal epithelium following incubation
in serum-free, vitamin A-deficient culture medium for 10 days, and if the effectiveness of a retinoid in reversing keratinization
in organ culture is correlated with its ability to compete for CRABP sites. The cytosol prepared from tracheal cultures contained
CRABP at a concentration of 2.61 pmoles per mg protein. Of the four retinoids with carboxyl end group selected for the study,
two of the biological active retinoids competed for the CRABP sites. However, no correlation was observed between the biological
activity of the inactive retinoids and their ability to associate with the CRABP sites. These results indicate that even though
the action of retinoid may be mediated by retinoid binding protein, it cannot be used as a sole predicator of retinoid response
in hamster trachea.
This investigation was supported by Contract N01-CP-31012 and U. S. P. H. Grants CA30512 and CA32428, which were awarded by
the Division of Cancer Etiology, National Cancer Institute, DHHS.
Editor's Statement Tracheal organ cultures provide a useful model for the study of epithelial differentiation and carcinogenesis.
Much attention has been given to the action of retinoids in this process. Mehta et al. demonstrate a lack of correlation between
biological activity and specific cytosolic binding of members of this class of compounds, pointing out the need for a more
complete biochemical understanding of the mechanism of action and active forms of retinoids in this and other systems in vivo
and in vitro. David W. Barnes 相似文献
110.
Banerjee S Mirsamadi N Anantharaman L Sivaram MV Gupta RB Choudhury D Roy RP 《The protein journal》2007,26(7):445-455
The identity of intermolecular contact residues in sickle hemoglobin (HbS) fiber is largely known. However, our knowledge
about combinatorial effects of two or more contact sites or the mechanistic basis of such effects is rather limited. Lys16,
His20, and Glu23 of the α-chain occur in intra-double strand axial contacts in the sickle hemoglobin (HbS) fiber. Here we
have constructed two novel double mutants, HbS (K16Q/E23Q) and (H20Q/E23Q), with a view to delineate cumulative impact of
interactions emanating from the above contact sites. Far-UV and visible region CD spectra of the double mutants were similar
to the native HbS indicating the presence of native-like secondary and tertiary structure in the mutants. The quaternary structures
in both the mutants were also preserved as judged by the derivative UV spectra of liganded (oxy) and unliganded (deoxy) forms
of the double mutants. However, the double mutants displayed interesting polymerization behavior. The polymerization behaviour
of the double mutants was found to be non-additive of the individual single mutants. While HbS (H20Q/E23Q) showed inhibitory
effect similar to that of HbS (E23Q), the intrinsic inhibitory propensity of the associated single mutants was totally quelled
in HbS (K16Q/E23Q) double mutant. Molecular dynamics (MD) simulations studies of the isolated α-chains as well as a module
of the fiber containing the double and associated single mutants suggested that these contact sites at the axial interface
of the fiber impact HbS polymerization through a coupled interaction network. The overall results demonstrate a subtle role
of dynamics and electrostatics in the polymer formation and provide insights about interaction-linkage in HbS fiber assembly. 相似文献