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971.
The X-ray repair cross complementing group 1 (XRCC1) protein is involved in DNA base excision repair and its expression varies during the cell cycle. Although studies have demonstrated that rapid XRCC1-dependent single-strand break repair (SSBR) takes place specifically during S/G(2) phases, it remains unclear how it is regulated during the cell cycle. We found that XRCC1 is a direct regulatory target of E2F1 and further investigated the role of XRCC1 in DNA repair during the cell cycle. Saos2 primary osteosarcoma cells stably transfected with inducible E2F1-wt or mutant E2F1-132E were treated with hydroxurea (HU) for 36h and were subsequently withdrawn HU for 2-24h to test whether cell-cycle-dependent DNA SSBR requires E2F1-mediated upregulation of XRCC1. We found that SSBR activity, as determined using a qPCR-base method, was correlated with E2F1 levels at different phases of the cell cycle. XRCC1-positive (AA8) and negative (EM9) CHO cells were used to demonstrate that the alterations in SSBR were mediated by XRCC1. The results indicate that E2F1-mediated regulation of XRCC1 is required for cell-cycle-dependent SSBR predominantly in G(1)/S phases. Our observations have provided new mechanistic insight for understanding the role of E2F1 in the maintenance of genomic stability and cell survival during the cell cycle. The regulation of XRCC1 by E2F1 during cell-cycle-dependent SSBR might be an important aspect for practical consideration for resolving the problem of drug resistance in tumor chemotherapies. 相似文献
972.
Deng Y Wong H Graham RA Liu W Shen HS Shi Y Wang L Meng M Malhi V Ding X Dean B 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2011,879(22):2119-2126
A rapid equilibrium dialysis (RED) assay followed by a solid phase extraction (SPE) high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) assay for the quantitative determination of unbound vismodegib in human plasma was developed and validated. The equilibrium dialysis was carried out using 0.3 mL plasma samples in the single-use plate RED system at 37°C for 6h. The dialysis samples (0.1 mL) were extracted using a Strata-X-C 33u Polymeric Strong Cation SPE plate and the resulting extracts were analyzed using reverse-phase chromatography and positive electrospray ionization (ESI) mass spectrometry. The standard curve, which ranged from 0.100 to 100 ng/mL for vismodegib, was fitted to a 1/x(2) weighted linear regression model. The lower limit of quantitation (LLOQ, 0.100 ng/mL) was sufficient to quantify unbound concentrations of vismodegib after dialysis. The intra-assay precision of the LC-MS/MS assay, based on the four analytical QC levels (LLOQ, low, medium and high), was within 7.7% CV and inter-assay precision was within 5.5% CV. The assay accuracy, expressed as %Bias, was within ±4.0% of the nominal concentration values. Extraction recovery of vismodegib was between 77.9 and 84.0%. The assay provides a means for accurate assessment of unbound vismodegib plasma concentrations in clinical studies. 相似文献
973.
Fei Gao Shi Fang Ding Mei Ni Chun Xi Liu Cheng Zhang Yun Zhang 《Journal of cellular and molecular medicine》2011,15(3):602-611
To test the hypothesis that combinatorial interference of toll-like receptor 2 (TLR2) and TLR4 is superior to isolated interference of TLR2 or TLR4 in stabilizing atherosclerotic plaques, lentiviruses carrying small interfering RNA of TLR2 or TLR4 were constructed and proved efficacious for knocking down mRNA and protein expression of TLR2 or TLR4 significantly in vitro. One hundred and fifty apolipoprotein E−/− mice fed a high-fat diet were divided into the control, mock, TLR2i, TLR4i and TLR2 + 4i subgroups and a constrictive collar was placed around carotid artery of these mice to induce plaque formation. TLR2i and TLR4i viral suspension was transfected into carotid plaques, respectively, in TLR2i and TLR4i subgroups, or in combination in TLR2 + 4i subgroup. Four weeks after lentivirus transfection, mRNA and protein expression of TLR2 or TLR4 was attenuated markedly in carotid plaques, leading to reduced local inflammatory cytokine expression and plaque content of lipid and macrophages, increased plaque content of collagen and lowered plaque vulnerability index. Factorial ANOVA analysis revealed that there was a synergistic effect between TLR4i and TLR2i in stabilizing plaques. In conclusion, combinatorial interference of TLR2 and TLR4 reduces local inflammation and stabilizes plaques more effectively than interference of TLR2 or TLR4 alone. 相似文献
974.
Wang J Mullighan CG Easton J Roberts S Heatley SL Ma J Rusch MC Chen K Harris CC Ding L Holmfeldt L Payne-Turner D Fan X Wei L Zhao D Obenauer JC Naeve C Mardis ER Wilson RK Downing JR Zhang J 《Nature methods》2011,8(8):652-654
We developed 'clipping reveals structure' (CREST), an algorithm that uses next-generation sequencing reads with partial alignments to a reference genome to directly map structural variations at the nucleotide level of resolution. Application of CREST to whole-genome sequencing data from five pediatric T-lineage acute lymphoblastic leukemias (T-ALLs) and a human melanoma cell line, COLO-829, identified 160 somatic structural variations. Experimental validation exceeded 80%, demonstrating that CREST had a high predictive accuracy. 相似文献
975.
Three new sesquiterpene acids, xylaric acids A-C (1-3, resp.), and a new tetralone (=3,4-dihydronaphthalen-1(2H)-one) derivative, 4, along with nine known compounds, xylaric acid D (5), hydroheptelidic acid (6), gliocladic acid (7), chlorine heptelidic acid (8), trichoderonic acid A (9), 16-(α-D-mannopyranosyloxy)isopimar-7-en-19-oic acid (10), 16-(α-D-glucopyranosyloxy)isopimar-7-en-19-oic acid (11), 5-carboxymellein (12), and naphthalen-1,8-diol 1-O-α-D-glucopyranoside (13) have been isolated from the solid culture of the ascomycete fungus Xylaria sp. associated with termite nest. The structures of these compounds were elucidated primarily by NMR experiments. The absolute configurations of compounds 1-3 and 5-9 were determined by combination of X-ray data and CD spectral analysis. The absolute configuration of 4 was assigned by Snatzke's method. Compounds 8 and 11 showed slight cytotoxicities against two cell lines A549 and SGC7901. 相似文献
976.
977.
John Melas‐Kyriazi I‐Kang Ding Arianna Marchioro Angela Punzi Brian E. Hardin George F. Burkhard Nicolas Tétreault Michael Grätzel Jacques‐E. Moser Michael D. McGehee 《Liver Transplantation》2011,1(3):407-414
A detailed investigation of the effect of hole transport material (HTM) pore filling on the photovoltaic performance of solid‐state dye‐sensitized solar cells (ss‐DSCs) and the specific mechanisms involved is reported. It is demonstrated that the efficiency and photovoltaic characteristics of ss‐DSCs improve with the pore filling fraction (PFF) of the HTM, 2,2’,7,7’‐tetrakis‐(N, N ‐di‐ p ‐methoxyphenylamine)9,9’‐spirobifluorene(spiro‐OMeTAD). The mechanisms through which the improvement of photovoltaic characteristics takes place were studied with transient absorption spectroscopy and transient photovoltage/photocurrent measurements. It is shown that as the spiro‐OMeTAD PFF is increased from 26% to 65%, there is a higher hole injection efficiency from dye cations to spiro‐OMeTAD because more dye molecules are covered with spiro‐OMeTAD, an order‐of‐magnitude slower recombination rate because holes can diffuse further away from the dye/HTM interface, and a 50% higher ambipolar diffusion coefficient due to an improved percolation network. Device simulations predict that if 100% PFF could be achieved for thicker devices, the efficiency of ss‐DSCs using a conventional ruthenium‐dye would increase by 25% beyond its current value. 相似文献
978.
Ding Haixia Zhang Jingsong Jiang Lei Dong Hairong Wang Jun Xiao Hang Chen Weixian 《Cell biochemistry and biophysics》2011,59(1):39-47
Extracellular domains of the transmembrane glycoprotein, neuropilin-1 (Np1), specifically bind an array of factors and co-receptors
including class-3 semaphorins (Sema3a), vascular endothelial growth factor (VEGF), hepatocyte growth factor, platelet-derived
growth factor BB, transforming growth factor-β 1 (TGF-β1), and fibroblast growth factor2 (FGF2). Np1 may have a role in immune
response, tumor cell growth, and angiogenesis, but its relative expression in comparison to its co-primary receptors, VEGF
and Sema3a, is not known. In this study we determined the mRNA expression of Np1 and its co-receptors, VEGF and Sema3a, and
the ratio of VEGF/Sema3a in different human and rodent cell lines. Expression of Np1, VEGF and Sema3a is very low in cells
derived from normal tissues, but these proteins are highly expressed in tumor-derived cells. Furthermore, the ratio of VEGF/Sema3a
is highly variable in different tumor cells. The elevated mRNA expression of Np1 and its putative receptors in tumor cells
suggests a role for these proteins in tumor cell migration and angiogenesis. As different tumor cells exhibit varying VEGF/Sema3a
ratios, it appears that cancer cells show differential response to angiogenic factors. These results bring to light the individual
variation among the cancer-related genes, Np1, VEGF, and Sema3a, and provide an important impetus for the possible personalized
therapeutic approaches for cancer patients. 相似文献
979.
Recurrent intracranial aneurysms can occur after either surgical clipping or endovascular therapy. In this article, we present
a consecutive series of 18 patients who underwent individual treatment for recurrent aneurysms after primary coil embolization
or surgical clipping. During an 8-year period between May 1997 and December 2005, 18 patients underwent individual treatment
for recurrent aneurysms. Clinical data and imaging studies of the patients were analyzed retrospectively. Out of the 18 patients,
13 had recurrent aneurysms located in the anterior circulation, and 5 had aneurysms of the posterior circulation. Treatment
consisted of coiling in 16 patients and clipping in two patients. Of the 18 patients, 15 achieved a good or excellent recovery,
two were paralyzed, and one died post-treatment. Both the surgical clipping and endovascular embolization for the treatment
of recurrent intracranial aneurysms can achieve very good radiological results with low mortality rates. One of the key points
for the successful treatment of this kind of lesions is the proper, individual, and interdisciplinary patient selection. 相似文献
980.
Liang Zhang Zhongyang Ding Peng Xu Yuhong Wang Zhenghua Gu Zhu Qian Guiyang Shi Kechang Zhang 《Biotechnology and Bioprocess Engineering》2011,16(3):457-461
Tyrosinase is a key enzyme in the biosynthesis of melanin, and the use of inhibitors against tyrosinase can prevent hyperpigmentation
by inhibiting enzymatic oxidation. However, the current use of tyrosine inhibitors is limited by their low activities and
high toxicities. The aim of the present research was to develop novel whitening agents, or tyrosinase-targeted medicine, from
a submerged culture of the fungus Ganoderma lucidum. Methyl lucidenate F was isolated from the ethanol-soluble-acidic components (ESACs) of G. lucidum, with the structure of ESACs elucidated via UV, LC-MS, and 13C-NMR spectral analysis. The tyrosinase inhibitory activity was measured using catechol as a substrate. Methyl lucidenate
F displayed uncompetitive inhibition of the potato tyrosinase activity, for which Lineweaver-Burk plots revealed a maximum
reaction rate (V
max) of 0.4367/min, Michaelis constant (K
m) of 6.765 mM and uncompetitive inhibition constant (K
i) of 19.22 μM. Meanwhile, methyl lucidenate F (tetra cyclic triterpenoid) exhibited high tyrosinase inhibitory activity, with
an IC50 of 32.23 μM. These results suggest that methyl lucidenate F may serve as a potential candidate for skin-whitening agents. 相似文献