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101.
Morphologic differentiation of colon carcinoma cell lines HT-29 and HT-29KM in rotating-wall vessels
Thomas J. Goodwin J. Milburn Jessup David A. Wolf 《In vitro cellular & developmental biology. Animal》1992,28(1):47-60
Summary A new low shear stress microcarrier culture system has been developed at NASA’s Johnson Space Center that permits three-dimensional
tissue culture. Two established human colon adenocarcinoma cell lines, HT-29, an undifferentiated, and HT-29KM, a stable,
moderately differentiated subline of HT-29, were grown in new tissue culture bioreactors called Rotating-Wall Vessels (RWVs).
RWVs are used in conjunction with multicellular cocultivation to develop a unique in vitro tissue modeling system. Cells were
cultivated on Cytodex-3 microcarrier beads, with and without mixed normal human colonic fibroblasts, which served as the mesenchymal
layer. Culture of the tumor lines in the absence of fibroblasts produced spheroidlike growth and minimal differentiation.
In contrast, when tumor lines were co-cultivated with normal colonic fibroblasts, initial growth was confined to the fibroblast
population until the microcarriers were covered. The tumor cells then commenced proliferation at an accelerated rate, organizing
themselves into three-dimensional tissue masses that achieved 1.0- to 1.5-cm diameters. The masses displayed glandular structures,
apical and internal glandular microvilli, tight intercellular junctions, desmosomes, cellular polarity, sinusoid development,
internalized mucin, and structural organization akin to normal colon crypt development. Differentiated samples were subjected
to transmission and scanning electron microscopy and histologic analysis, revealing embryoniclike mesenchymal cells lining
the areas around the growth matrices. Necrosis was minimal throughout the tissue masses. These data suggest that the RWV affords
a new model for investigation and isolation of growth, regulatory, and structural processes within neoplastic and normal tissue. 相似文献
102.
Walter M. Fitch 《Journal of molecular evolution》1981,18(1):30-37
Summary A procedure is presented that forms an unrooted tree-like structure from a matrix of pairwise differences. The tree is not formed a portion at a time, as methods now in use generally do, but is formed en toto without intervening estimates of branch lengths. The method is based on a relaxed additivity (four-point metric) constraint. From the tree, a classification may be formed. 相似文献
103.
Developing desorption isotherms for inorganic phosphorus (P) is a time-consuming and non-standardized procedure. Anion exchange
membranes (AEMs) have been successfully used in studies of P desorption kinetics and total membrane-desorbable P, but rarely
have they been used for developing P desorption isotherms. Our study had two objectives: (1) to evaluate the suitability of
using multiple strips of AEMs (termed the Multiple AEM Method) to develop P desorption isotherms; and (2) to compare the Multiple
AEM Method with a sequential-extraction approach using AEMs (termed the Sequential AEM Method) to determine if the manner
in which AEMs were used would influence the slope of the desorption isotherm, i.e. the partition coefficient. Both methods
yielded well-defined, but numerically different desorption isotherms for all levels of sorbed P. However, estimated K
d
values among methods were equivalent in the low and medium levels of P sorbed. The Multiple AEM method was quicker than the
Sequential AEM method, but both gave similar K
d
values in an agriculturally significant range of soil solution concentrations. These methods should be tested on a range
of soil type to determine their suitability in developing P desorption isotherms and to move toward method standardization
for desorption isotherms. 相似文献
104.
Acetabular dysplasia is a known cause of hip osteoarthritis. In addition to abnormal anatomy, changes in kinematics, joint reaction forces (JRFs), and muscle forces could cause tissue damage to the cartilage and labrum, and may contribute to pain and fatigue. The objective of this study was to compare lower extremity joint angles, moments, hip JRFs and muscle forces during gait between patients with symptomatic acetabular dysplasia and healthy controls. Marker trajectories and ground reaction forces were measured in 10 dysplasia patients and 10 typically developing control subjects. A musculoskeletal model was scaled in OpenSim to each subject and subject-specific hip joint centers were determined using reconstructions from CT images. Joint kinematics and moments were calculated using inverse kinematics and inverse dynamics, respectively. Muscle forces and hip JRFs were estimated with static optimization. Inter-group differences were tested for statistical significance (p ≤ 0.05) and large effect sizes (d ≥ 0.8). Results demonstrated that dysplasia patients had higher medially directed JRFs. Joint angles and moments were mostly similar between the groups, but large inter-group effect sizes suggested some restriction in range of motion by patients at the hip and ankle. Higher medially-directed JRFs and inter-group differences in hip muscle forces likely stem from lateralization of the hip joint center in dysplastic patients. Joint force differences, combined with reductions in range of motion at the hip and ankle may also indicate compensatory strategies by patients with dysplasia to maintain joint stability. 相似文献
105.
The increasing resistance of pathogens to common antibiotics, as well as the need to control urease activity to improve the yield of soil nitrogen fertilization in agricultural applications, has stimulated the development of novel classes of molecules that target urease as an enzyme. In this context, the newly developed compounds on the basis of 1-heptanoyl-3-arylthiourea family were evaluated for Jack bean urease enzyme inhibition activity to validate their role as potent inhibitors of this enzyme. 1-Heptanoyl-3-arylthioureas were obtained in excellent yield and characterized through spectral and elemental analysis. All the compounds displayed remarkable potency against urease inhibition as compared to thiourea standard. It was found that novel compounds fulfill the criteria of drug-likeness by obeying Lipinski’s rule of five. Particularly compound 4a and 4c can serve as lead molecules in 4D (drug designing discovery and development). Kinetic mechanism and molecular docking studies also carried out to delineate the mode of inhibition and binding affinity of the molecules. 相似文献
106.
The design and synthesis of a new series of 1,4-dihydroquinazolin-3(2H)-yl benzamide derivatives (4a–o) as anti-inflammatory and analgesic agents and COX-1/2 inhibitors are reported. The target compounds (4a–o) were synthesized using a two-step scheme, and their chemical structures were confirmed with 1H NMR, 13C NMR, and mass spectra and elemental analysis. Compounds 4b, 4d, 4h, 4l, 4n and 4o showed the best in vitro COX-2 inhibitory activity (IC50 0.04–0.07 μM), which was nearly the same as that of the reference drug celecoxib (IC50 0.049 μM), but had a lower selectivity index, as dictated in our target design. In the in vivo anti-inflammatory inhibition assay, compounds 4b, 4c, 4e, 4f, 4m and 4o showed better oedema inhibition percentages, ranging from 38.1% to 54.1%, than did diclofenac sodium (37.8%). An in vivo analgesic assay revealed that compounds 4b and 4n had a potential analgesic effect 4- to 21-fold more potent than that of indomethacin and diclofenac sodium. All the tested compounds showed an improved ulcerogenic index when compared to indomethacin. In the synthesized series, compound 4b showed the best biological activity in all the experiments. The docking study results agreed with the in vitro COX inhibition assay results. Moreover, the predicted in silico studies of all the compounds support their potential as drug candidates. 相似文献
107.
《Bioorganic & medicinal chemistry》2014,22(7):2052-2059
In our continuous efforts to identify novel potent HIV-1 NNRTIs, a novel class of 5,7-disubstituted pyrazolo[1,5-a]pyrimidine derivatives were rationally designed, synthesized and evaluated for their anti-HIV activities in MT4 cell cultures. Biological results showed that most of the tested compounds displayed excellent activity against wild-type HIV-1 with a wide range of EC50 values from 5.98 to 0.07 μM. Among the active compounds, 5a was found to be the most promising analogue with an EC50 of 0.07 μM against wild-type HIV-1 and very high selectivity index (SI, 3999). Compound 5a was more effective than the reference drugs nevirapine (by 2-fold) and delavirdine (by 2-fold). In order to further confirm their binding target, an HIV-1 RT inhibitory assay was also performed. Furthermore, SAR analysis among the newly synthesized compounds was discussed and the binding mode of the active compound 5a was rationalized by molecular modeling studies. 相似文献
108.
Based on the high-resolution X-ray crystallographic structure of phospholipase C from Bacillus cereus, the orientation of the phosphatidylcholine substrate in the active site of the enzyme is proposed. The proposal is based on extensive calculations using the GRID program and molecular mechanics geometry relaxations. The substrate model has been constructed by successively placing phosphate, choline and diacylglycerol moieties in the positions indicated from GRID calculations. On the basis of the resulting orientation of a complete phosphatidylcholine molecule, we propose a mechanism for the hydrolysis of the substrate. 相似文献
109.
Bornali Chakrabarti Hridoy R Bairagya Deepak Kr Mishra Pradip Kumar Chatterjee Bishnu P Mukhopadhyay 《Bioinformation》2013,9(3):126-133
Human matrix metalloproteinase-8 (hMMP-8) plays a important role in the progression of colorectal cancer, metastasis, multiple
sclerosis and rheumetoid arthritis. Extensive MD-simulation of the PDB and solvated structures of hMMP-8 has revealed the
presence of few conserved water molecules around the catalytic and structural zinc (ZnC and ZnS) ions. The coordination of two
conserved water molecules (W and WS) to ZnS and the H-bonding interaction of WS to S151 have indicated the plausible involvement
of that metal ion in the catalytic process. Beside this the coupling of ZnC and ZnS metal ions (ZnC – WH (W1)…..W2 ….H162 - ZnS)
through two conserved hydrophilic centers (occupied by water molecules) may also provide some rational on the recognition of
two zinc ions which were separated by ~13 Å in their X-ray structures. This unique recognition of both the Zn+2 ions in the enzyme
through conserved water molecules may be implemented/ exploited for the design of antiproteolytic agent using water mimic
drug design protocol. 相似文献
110.
Elmar Porten Beate Seliger Verena A. Schneider Stefan W?ll Daniela Stangel Rene Ramseger Stephan Kr?ger 《The Journal of biological chemistry》2010,285(5):3114-3125
Clustering or overexpression of the transmembrane form of the extracellular matrix proteoglycan agrin in neurons results in the formation of numerous highly motile filopodia-like processes extending from axons and dendrites. Here we show that similar processes can be induced by overexpression of transmembrane-agrin in several non-neuronal cell lines. Mapping of the process-inducing activity in neurons and non-neuronal cells demonstrates that the cytoplasmic part of transmembrane agrin is dispensable and that the extracellular region is necessary for process formation. Site-directed mutagenesis reveals an essential role for the loop between β-sheets 3 and 4 within the Kazal subdomain of the seventh follistatin-like domain of TM-agrin. An aspartic acid residue within this loop is critical for process formation. The seventh follistatin-like domain could be functionally replaced by the first and sixth but not by the eighth follistatin-like domain, demonstrating a functional redundancy among some follistatin-like domains of agrin. Moreover, a critical distance of the seventh follistatin-like domain to the plasma membrane appears to be required for process formation. These results demonstrate that different regions within the agrin protein are responsible for synapse formation at the neuromuscular junction and for process formation in central nervous system neurons and suggest a role for agrin''s follistatin-like domains in the developing central nervous system. 相似文献