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891.
Understanding the mechanisms of inhibitors of translation termination may inform development of new antibacterials and therapeutics for premature termination diseases. We report the crystal structure of the potent termination inhibitor blasticidin S bound to the ribosomal 70S?release factor 1 (RF1) termination complex. Blasticidin S shifts the catalytic domain 3 of RF1 and restructures the peptidyl transferase center. Universally conserved uridine 2585 in the peptidyl transferase center occludes the catalytic backbone of the GGQ motif of RF1, explaining the structural mechanism of inhibition. Rearrangement of domain 3 relative to the codon-recognition domain 2 provides insight into the dynamics of RF1 implicated in termination accuracy. 相似文献
892.
Paced QRS morphology predicts incident left ventricular systolic dysfunction and atrial fibrillation
Martin van Zyl Chance M. Witt Subir Bhatia Majd Khasawneh Prakriti Gaba Charles J. Lenz Andrew N. Rosenbaum Htin Aung David O. Hodge Christopher J. McLeod Samuel J. Asirvatham 《Indian pacing and electrophysiology journal》2019,19(2):40-46
Background
The prognostic significance of paced QRS complex morphology on surface ECG remains unclear. This study aimed to assess long-term outcomes associated with variations in the paced QRS complex.Methods
Adult patients who underwent dual-chamber pacemaker implantation with 20% or more ventricular pacing and a 12-lead ECG showing a paced complex were included. The paced QRS was analyzed in leads I and aVL. Long-term clinical and echocardiographic outcomes were compared at 5 years.Results
The study included 844 patients (43.1% female; age 75.0?±?12.1). Patients with a longer paced QRS (pQRS) duration in lead I had a lower rate of atrial fibrillation (HR 0.80; p?=?0.03) and higher rate of systolic dysfunction (HR 1.17; p?<?0.001). Total pacing complex (TPC) duration was linked to higher rates of ICD implantation (HR 1.18; p?=?0.04) and systolic dysfunction (HR 1.22, p?<?0.001). Longer paced intrinsicoid deflection (pID) was associated with less atrial fibrillation (HR 0.75; p?=?0.01), more systolic dysfunction (HR 1.17; p?<?0.001), ICD implantation (HR 1.23; p?=?0.04), and CRT upgrade (HR 1.23; p?=?0.03). Exceeding thresholds for TPC, pQRS, and pID of 170, 146, and 112?ms in lead I, respectively, was associated with a substantial increase in systolic dysfunction over 5 years (p?<?0.001).Conclusions
Longer durations of all tested parameters in lead I were associated with increased rates of left ventricular systolic dysfunction. ICD implantation and CRT upgrade were also linked to increased TPC and pID durations. Paradoxically, patients with longer pID and pQRS had less incident atrial fibrillation. 相似文献893.
894.
Keiko Tadano-Aritomi Harumi Kubo Philip Ireland Takeshi Kasama Shizuo Handa Ineo Ishizuka 《Glycoconjugate journal》1996,13(2):285-293
A novel mono-sulfated glycosphingolipid based on the gangliotriaose core structure was isolated from rat kidney. The isolation procedure involved extraction of lipids with chloroform/methanol, mild alkaline methanolysis, column chromatographies with anion exchangers and silica beads. The structure was characterized by compositional analysis, FTIR spectroscopy, methylation analysis,1H-NMR spectroscopy and negative-ion liquid secondary ion mass spectrometry (LSIMS) using the intact glycolipid and its desulfation product. The two dimensional chemical shift correlated spectroscopy provided information on the sugar sequence as well as anomeric configurations, and indicated the presence of a 3-O-sulfatedN-acetylgalactosamine within the molecule. Negative-ion LSIMS with high- and low-energy collision-induced dissociation defined the sugar sequence and ceramide composition, confirming the presence of a sulfatedN-acetylgalactosamine at the non-reducing terminus. From these results, the complete structure was proposed to be HSO3-3GalNAc1-4Gal1-4Glc1-1Cer (Gg3Cer III3-sulfate, SM2b).
Abbreviations: Abbreviations for sulfated glycolipids [17] follow the modifications of the nomenclature system of Svennerholm for gangliosides [37], and the designation of the other glycosphingolipids follows the IUPAC-IUB recommendations [38]. Cer, ceramide; LacCer, lactosylceramide, Gal1-4Glc1-1Cer; Gg3Cer, gangliotriaosylceramide, GalNAc1-4Gal1-4Glc1-1Cer; Gg4Cer, gangliotetraosylceramide, Gal1-3GalNAc1-4Gal1-4Glc1-1Cer; iGb4Cer, isoglobotetraosylceramide, GalNAc1-3Gal1-3Gal1-4Glc1-1Cer; Gb4Cer, globotetraosylceramide, GalNAc1-3Gal1-4Gal1-4Glc1-1Cer; SM4s, galactosylceramide sulfate, GalCer I3-sulfate; SM3, lactosylceramide sulfate, LacCer II3-sulfate; SM2a, Gg3Cer II3-sulfate; SM2b, Gg3Cer III3-sulfate; SB2, Gg3Cer II3,III3-bis-sulfate; SM1a, Gg4Cer II3-sulfate; SM1b, Gg4Cer IV3-sulfate; SB1a, Gg4Cer II3,IV3-bissulfate; GLC, gas-liquid chromatography; GC-MS, gas chromatography-mass spectrometry; DQF, double quantum filtered; COSY, chemical-shift-correlated spectroscopy; LSIMS, liquid secondary ion mass spectrometry; CID, collision-induced dissociation; MS/MS, tandem mass spectrometry. 相似文献
895.
J. ?stling J.-P. Cassart J. Vandenhaute H. Ronne 《Molecular & general genetics : MGG》1998,260(2-3):269-279
The Mig1 repressor is a zinc finger protein that mediates glucose repression in yeast. Previous work in Saccharomyces cerevisiae has shown that two domains in Mig1p are required for repression: the N-terminal zinc finger region and a C-terminal effector
domain. Both domains are also conserved in Mig1p homologs from the distantly related yeasts Kluyveromyces lactis and K. marxianus, and these Mig1 proteins can fully replace the endogenous Mig1p in S. cerevisiae. We have now made a detailed analysis of the conserved C-terminal effector domain in Mig1p from K. marxianus, using expression in S. cerevisiae to monitor its function. First, a series of small deletions were made within the effector domain. Second, an alanine scan
mutagenesis was carried out across the effector domain. Third, double, triple and quadruple mutants were made that affect
certain residues within the effector domain. Our results show that four conserved residues within the effector domain, three
leucines and one isoleucine, are particularly important for its function in vivo. The analysis further revealed that while
the C-terminal effector domain of KmMig1p mediates a seven- to nine-fold repression of the reporter gene, a five- to sixfold
residual effect also exists that is independent of the C-terminal effector domain. Similar results were obtained when the
corresponding mutations were made in ScMig1p. Moreover, we found that mutations in these residues affect the interaction between
Mig1p and the general corepressor subunit Cyc8p (Ssn6p). Modeling of the C-terminal effector domain using a protein of known
structure suggests that it may be folded into an α-helix.
Received: 30 March 1998 / Accepted: 18 August 1998 相似文献
896.
897.
Albright Craig D. Tsai Amy Y. Mar Mei-Heng Zeisel Steven H. 《Neurochemical research》1998,23(5):751-758
Choline availability influences long-term memory in concert with changes in the spatial organization and morphology of septal neurons, however little is known concerning the effects of choline on the hippocampus, a region of the brain also important for memory performance. Pregnant rats on gestational day 12 were fed a choline control (CT), choline supplemented (CS), or choline deficient (CD) diet for 6 days and fetal brain slices were prepared on embryonic day 18 (El8). The hippocampus in these brain slices was studied for the immunohistochemical localization of the growth-related proteins transforming growth factor beta type 1 (TGF1) and GAP43, the cytoskeletal proteins vimentin and microtubule associated protein type 1 (MAP1), and the neuronal cell marker neuron specific enolase (NSE). In control hippocampus, there was weak expression of TGF1 and vimentin proteins, but moderately intense expression of MAP1 protein. These proteins were not homogeneously distributed, but were preferentially localized to cells with large cell bodies located in the central (CA1–CA3) region of the hippocampus, and to the filamentous processes of small cells in the fimbria region. Feeding a choline-supplemented diet decreased, whereas a choline-deficient diet increased the intensity of immunohistochemical labeling for these proteins in El8 hippocampus. GAP43 and NSE were localized to peripheral nervous tissue but not hippocampus, indicating that the maturation of axons and neurite outgrowth in embryonic hippocampus were unaffected by the availability of choline in the diet. These data suggest that the availability of choline affects the differentiation of specific regions of developing hippocampus. 相似文献
898.
899.
900.
M Cohn 《Biochimie》1985,67(1):9-27
Two concepts of the evolution and regulation of expression of the combining site repertoire of the immune system, are compared. One view is based on the Associative Recognition Theory as formulated by the author and the other is based on the Idiotype Network Idea as conceived by Jerne. The two concepts are analyzed from the point of view of their logic, internal consistency and factual support. 相似文献