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51.
E. Chiarpotto F. Biasi M. Aragno A. Scavazza O. Danni E. Albano G. Poli 《Cell biochemistry and function》1993,11(1):71-75
The combination of carbon tetrachloride (CCl4) and 1,2-dibromoethane (DBE) in isolated rat hepatocytes led to a significant potentiation of both lipid peroxidation and of plasma membrane damage observed after a single treatment with CCl4. Such a synergistic effect appeared to be related to the CCl4-induced shift of DBE metabolism from the cytosolic conjugation with glutathione towards the microsomal transformation into toxic intermediates. In fact, CCl4 significantly inactivated hepatocyte total GSH-transferase, i.e. the DBE detoxification pathway. Furthermore, while the microsomal metabolism of CCl4 was not affected by the simultaneous presence of DBE, the amount of DBE reactive metabolities covalently bound to hepatocyte protein was significantly enhanced in the presence of CCl4. 相似文献
52.
Summary Paleozoic carbonate ramp sedimentation has generally been described in terms of downlapping clinoforms composed of allochthonous
sediment derived from shallower environments. However, during transgressive episodes when carbonate sediment production is
low and down slope sediment transport by gravity becomes inactive, autochthonous carbonate sediment accumulates in vertical
stacks of essentially in situ sediment. Autochthonous outer ramp deposition is probably a part of many Paleozoic ramp strata,
but has heretofore not been recognized because of the general absence of adequate exposures.
Evidence of autochthonous, in situ deposition and preservation of sediments in a starved setting is well displayed in the
Alamogordo Member of the Lake Valley Formation in south central New Mexico. This evidence includes: 1) beds and bed sets that
are individually continuous and traceable along ramp slope for 32 km, 2) down-ramp sequential distributions of depth-sensitive
organisms and assemblages but patchy distribution of rock types, 3) lack of sedimentary structures indicative of transport,
4) well preserved, unabraded fossils, 5) the common occurrence of fossils in life position, 6) beds traceable into and through
mounds 7) bed thickness trends ascribed to biotic productivity, and 8) geopetal structures in original position.
Integrated paleontologic, sedimentologic, and stratigraphic data provide information about depositional processes and setting.
The depositional slope was approximately 0.5o based on the distribution of fossil algae; this is comparable to dips reported for other Mississippian homoclinal ramps.
An oxygen minimum zone may have impinged on the ramp during a major flooding event. Shifts in biotic gradients from bed to
bed reveal transgressive-regressive patterns that would not be resolvable without detailed paleontological evidence.
The Alamogordo Member formed as a result of transgressive and early highstand starved carbonate sedimentation along a narrow,
homoclinal outer ramp. The surface of maximum flooding and the boundary between the TST and HST are within the Alamogordo
Member. 相似文献
53.
《Neurochemistry international》1995,26(6):635-641
Acetylcholine synthesis from radiolabelled glucose was monitored in cerebral cortex cells isolated from brains of suckling and adult rats. Acetylcholine synthesis was found much higher in suckling animals, both in the absence and presence of acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) inhibitor, paraoxon. Together with choline (20 μM), carnitine was found to stimulate acetylcholine synthesis in a synergistic way in cortex cells from adult rats (18%). Choline, however, was incapable of reversing an inhibitory effect exerted by carnitine on acetylcholine synthesis in cortex cells from suckling animals. Distribution of carnitine derivatives was found significantly different in the cells from young and old animals, the content of acetylcarnitine decreased with age with a corresponding increase of free carnitine. The observed differences in carnitine effect on acetylcholine synthesis suggested that high acetylcarnitine in cells capable of β-oxidation might be correlated with the lower level of acetylcholine synthesis. 相似文献
54.
BackgroundThere is a crucial need for finding and developing new compounds as the anticancer and antimicrobial agents with better activity, specific target, and less toxic side effects.ObjectivesBase on the potential anticancer properties of lanthanide complexes, in the paper, the biological applications of terbium (Tb) complex, containing 2,9-dimethyl- 1,10-phenanthroline (Me2Phen) such as anticancer, antimicrobial, DNA cleavage ability, the interaction with FS-DNA (Fish-Salmon DNA) and BSA (Bovine Serum Albumin) was examined.MethodsThe interaction of Tb-complex with BSA and DNA was studied by emission spectroscopy, absorption titration, viscosity measurement, CD spectroscopy, competitive experiments, and docking calculation. Also, the ability of this complex to cleave DNA was reported by gel electrophoresis. Tb-complex was concurrently screened for its antibacterial activities by different methods. Besides, the nanocarriers of Tb-complex (lipid nanoencapsulation (LNEP) and the starch nanoencapsulation (SNEP)), as active anticancer candidates, were prepared. MTT technique was applied to measure the antitumor properties of these compounds on human cancer cell lines.ResultsThe experimental and docking results suggest significant binding between DNA as well as BSA with terbium-complex. Besides, groove binding plays the main role in the binding of this compound with DNA and BSA. The competitive experiment with hemin demonstrated that the terbium complex was bound at site III of BSA, which was confirmed by the docking study. Also, Tb-complex was concurrently screened for its DNA cleavage, antimicrobial, and anticancer activities. The anticancer properties of LNEP and SNEP are more than the terbium compound.ConclusionsTb-complex can bond to DNA/BSA with high binding affinity. Base on biological applications of Tb-complex, it can be concluded that this complex and its nanocarriers can suggest as novel anticancer, antimicrobial candidates. 相似文献
55.
The study of pediatric head injury relies heavily on the use of finite element models and child anthropomorphic test devices (ATDs). However, these tools, in the context of pediatric head injury, have yet to be validated due to a paucity of pediatric head response data. The goal of this study is to investigate the response and injury tolerance of the pediatric head to impact.Twelve pediatric heads were impacted in a series of drop tests. The heads were dropped onto five impact locations (forehead, occiput, vertex and right and left parietal) from drop heights of 15 and 30 cm. The head could freely fall without rotation onto a flat 19 mm thick platen. The impact force was measured using a 3-axis piezoelectric load cell attached to the platen.Age and drop height were found to be significant factors in the impact response of the pediatric head. The head acceleration (14%–15 cm; 103–30 cm), Head Injury Criterion (HIC) (253%–15 cm; 154%–30 cm) and impact stiffness (5800%–15 cm; 3755%–30 cm) when averaged across all impact locations increased with age from 33 weeks gestation to 16 years, while the pulse duration (66%–15 cm; 53%–30 cm) decreased with age. Increases in head acceleration, HIC and impact stiffness were also observed with increased drop height, while pulse duration decreased with increased drop height.One important observation was that three of the four cadaveric heads between the ages of 5-months and 22-months sustained fractures from the 15 cm and 30 cm drop heights. The 5-month-old sustained a right parietal linear fracture while the 11- and 22-month-old sustained diastatic linear fractures. 相似文献
56.
《Current biology : CB》2020,30(13):2433-2445.e3
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57.
《Bioorganic & medicinal chemistry》2020,28(24):115819
The exploitation of GLU988 and LYS903 residues in PARP1 as targets to design isoquinolinone (I & II) and naphthyridinone (III) analogues is described. Compounds of structure I have good biochemical and cellular potency but suffered from inferior PK. Constraining the linear propylene linker of structure I into a cyclopentene ring (II) offered improved PK parameters, while maintaining potency for PARP1. Finally, to avoid potential issues that may arise from the presence of an anilinic moiety, the nitrogen substituent on the isoquinolinone ring was incorporated as part of the bicyclic ring. This afforded a naphthyridinone scaffold, as shown in structure III. Further optimization of naphthyridinone series led to identification of a novel and highly potent PARP1 inhibitor 34, which was further characterized as preclinical candidate molecule. Compound 34 is orally bioavailable and displayed favorable pharmacokinetic (PK) properties. Compound 34 demonstrated remarkable antitumor efficacy both as a single-agent as well as in combination with chemotherapeutic agents in the BRCA1 mutant MDA-MB-436 breast cancer xenograft model. Additionally, compound 34 also potentiated the effect of agents such as temozolomide in breast cancer, pancreatic cancer and Ewing’s sarcoma models. 相似文献
58.
59.
《Bioorganic & medicinal chemistry》2020,28(9):115437
NDM-1 can hydrolyze nearly all available β-lactam antibiotics, including carbapenems. NDM-1 producing bacterial strains are worldwide threats. It is still very challenging to find a potent NDM-1 inhibitor for clinical use. In our study, we used a metal-binding pharmacophore (MBP) enriched virtual fragment library to screen NDM-1 hits. SPR screening helped to verify the MBP virtual hits and identified a new NDM-1 binder and weak inhibitor A1. A solution NMR study of 15N-labeled NDM-1 showed that A1 disturbed all three residues coordinating the second zinc ion (Zn2) in the active pocket of NDM-1. The perturbation only happened in the presence of zinc ion, indicating that A1 bound to Zn2. Based on the scaffold of A1, we designed and synthesized a series of NDM-1 inhibitors. Several compounds showed synergistic antibacterial activity with meropenem against NDM-1 producing K. pneumoniae. 相似文献
60.
Many lung disease processes are characterized by structural and functional heterogeneity that is not directly appreciable with traditional physiological measurements. Experimental methods and lung function modeling to study regional lung function are crucial for better understanding of disease mechanisms and for targeting treatment. Synchrotron radiation offers useful properties to this end: coherence, utilized in phase-contrast imaging, and high flux and a wide energy spectrum which allow the selection of very narrow energy bands of radiation, thus allowing imaging at very specific energies. K-edge subtraction imaging (KES) has thus been developed at synchrotrons for both human and small animal imaging. The unique properties of synchrotron radiation extend X-ray computed tomography (CT) capabilities to quantitatively assess lung morphology, and also to map regional lung ventilation, perfusion, inflammation and biomechanical properties, with microscopic spatial resolution. Four-dimensional imaging, allows the investigation of the dynamics of regional lung functional parameters simultaneously with structural deformation of the lung as a function of time. This review summarizes synchrotron radiation imaging methods and overviews examples of its application in the study of disease mechanisms in preclinical animal models, as well as the potential for clinical translation both through the knowledge gained using these techniques and transfer of imaging technology to laboratory X-ray sources. 相似文献