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991.
Ma J Zhang L Han W Shen T Ma C Liu Y Nie X Liu M Ran Y Zhu D 《Journal of lipid research》2012,53(6):1093-1105
Pulmonary artery endothelial plexiform lesion is responsible for pulmonary vascular remodeling (PVR), a basic pathological change of pulmonary arterial hypertension (PAH). Recent evidence suggests that epoxyeicosatrienoic acid (EET), which is derived from arachidonic acid by cytochrome p450 (CYP) epoxygenase, has an essential role in PAH. However, until now, most research has focused on pulmonary vasoconstriction; it is unclear whether EET produces mitogenic and angiogenic effects in pulmonary artery endothelial cells (PAEC). Here we found that 500 nM/l 8,9-EET, 11,12-EET, and 14,15-EET markedly augmented JNK and c-Jun activation in PAECs and that the activation of c-Jun was mediated by JNK, but not the ERK or p38 MPAK pathway. Moreover, treatment with 8,9-EET, 11,12-EET, and 14,15-EET promoted cell proliferation and cell-cycle transition from the G0/G1 phase to S phase and stimulated tube formation in vitro. All these effects were reversed after blocking JNK with Sp600125 (a JNK inhibitor) or JNK1/2 siRNA. In addition, the apoptotic process was alleviated by three EET region isomers through the JNK/c-Jun pathway. These observations suggest that 8,9-EET, 11,12-EET, and 14,15-EET stimulate PAEC proliferation and angiogenesis, as well as protect the cells from apoptosis, via the JNK/c-Jun pathway, an important underlying mechanism that may promote PAEC growth and angiogenesis during PAH. 相似文献
992.
Watanabe S Tan KH Rathore AP Rozen-Gagnon K Shuai W Ruedl C Vasudevan SG 《Journal of virology》2012,86(10):5508-5514
There are conflicting data on the relationship between the level of secreted NS1 (sNS1), viremia, and disease severity upon dengue virus (DENV) infection in the clinical setting, and therefore, we examined this relationship in the widely accepted AG129 mouse model. Because of the failure of a routinely used NS1 detection kit to detect sNS1 of the mouse-adapted DENV2 strain, we screened 15 previously undescribed NS1 monoclonal antibodies and developed a robust capture enzyme-linked immunosorbent assay (ELISA) with detection sensitivity at the low nanogram level (0.2 ng/ml) using recombinant baculovirus-expressed sNS1 as well as sNS1 that was immunoaffinity purified from the various DENV2 strains employed in this study. Using this test, we demonstrated that increased viremia paralleled severe pathologies; however, sNS1 level did not correlate with viremia or severity. Furthermore, among the DENV2 strains that were tested, the level of NS1 secretion did not correspond to virus replication rate in vitro, at the cellular level. Together, our data indicate that the magnitude of NS1 secretion appears to be strain dependent and does not correlate with viral virulence in the AG129 mouse model. 相似文献
993.
We report the full-genome sequence of a goose-origin reovirus (GRV) strain 03G from Zhejiang Province, China. This is the first report of the complete genomic sequence (segments 1 to 10) of GRV. Phylogenetic analyses of the sequence suggest that GRV 03G represents a new species distinct from other established species within the avian reovirus (ARV) group of orthoreoviruses. 相似文献
994.
Widdrol is an odorant compound isolated from Juniperus chinensis. We previously reported that widdrol induces Gap 1 (G1) phase cell cycle arrest and leads to apoptosis in human colon adenocarcinoma HT29 cells. It was also reported that this cell cycle arrest is associated with the induction of checkpoint kinase 2 (Chk2), p53 phosphorylation and cyclin dependent kinase (Cdk) inhibitor p21 expression. In this paper, we investigated the molecular mechanisms of widdrol on the activation of G1 DNA damage checkpoint at early phase when DNA damages occurred in HT29 cells. First of all, we examined that widdrol breaks DNA directly or not. As the results of DNA electrophoresis and formation of phosphorylated histone H2AX (γH2AX) foci in HT29 cells, widdrol generates DNA double-strand breaks directly within 0.5?h both in vitro and in vivo. Based on this result, the change of proteins related in checkpoint pathway was examined over a time course of 0.5-24?h. Treatment of HT29 cells with widdrol elicits the following: (1) phosphorylation of Chk2 and p53, (2) reduction of cell division cycle 25A (Cdc25A) expression, (3) increase of Cdk inhibitor p21 expression, and (4) decrease of the levels of Cdk2 and cyclin E expression in a time-dependent manner. Moreover, only the expression level of mini-chromosome maintenance 4 (MCM4) protein, a subunit of the eukaryotic DNA replicative helicase, is rapidly down-regulated in HT29 cells treated with widdrol over the same time course, but those of the other MCM proteins are unchanged. Overall, our results indicated that widdrol breaks DNA directly in HT29 cells, and this DNA damage results in checkpoint activation via Chk2-p53-Cdc25A-p21-MCM4 pathway and finally cells go to G1-phase cell cycle arrest and apoptosis. 相似文献
995.
Wei R Zhang Y Shen L Jiang W Li C Zhong M Xie Y Yang D He L Zhou Q 《Molecular and cellular biochemistry》2012,359(1-2):151-159
In clinic, many non-small cell lung cancer (NSCLC) patients receive radiation therapy after chemotherapy failure. However, whether the multidrug resistance (MDR) can elevate the radioresistance (RDR) remains unclear. To evaluate the MDR's effect on the RDR, screen MDR- and RDR-related proteins in human lung adenocarcinoma (HLA) cells and tissues A549, and A549/DDP cells after irradiation were analyzed by colony-forming assay and flow cytometry. Two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) were utilized to identify differentially expressed proteins (DEPs) between them. The value of D0, Dq, and SF2 increased, the mean percentage in G2 phase and apoptosis rate significantly decreased in A549/DDP cells compared with A549 cells. 40 DEP points were found, and among them 27 were identified through proteomics. Four up-regulated proteins (HSPB1, Vimentin, Cofilin-1, and Annexin A4) in MDR cells compared with non-MDR cells, were confirmed by Western blot. Immuno-histochemistry showed that they were also over-expressed in MDR tissues compared with non-MDR counterparts of HLA. These results proved that the MDR in HLA cells and tissues increased the RDR. HSPB1, Vimentin, Cofilin-1, and Annexin A4 are potential biomarkers for predicting HLA response to MDR and RDR, and novel treatment targets of HLA. 相似文献
996.
997.
Ha YM Park YJ Lee JY Park D Choi YJ Lee EK Kim JM Kim JA Park JY Lee HJ Moon HR Chung HY 《Biochimie》2012,94(2):533-540
Herein we describe the design, synthesis and biological activities of 2-(substituted phenyl)thiazolidine-4-carboxylic acid derivatives as novel tyrosinase inhibitors. The target compounds 2a–2j were designed and synthesized from the structural characteristics of N-phenylthiourea, tyrosinase inhibitor and tyrosine, and l-DOPA, the natural substrates of tyrosinase. Among them, (2R/S,4R)-2-(2,4-dimethoxyphenyl)thiazolidine-4-carboxylic acid (2g) caused the greatest inhibition 66.47% at 20 μM of l-DOPA oxidase activity of mushroom tyrosinase. Kinetic analysis of tyrosinase inhibition revealed that 2g is a competitive inhibitor. We predicted the tertiary structure of tyrosinase, and simulated the docking of mushroom tyrosinase with 2g. These results suggest that the binding affinity of 2g with tyrosinase is high. Also, 2g effectively inhibited tyrosinase activity and reduced melanin levels in B16 cells treated with α-MSH. These data strongly suggest that 2g can suppress the production of melanin via the inhibition of tyrosinase activity. 相似文献
998.
Guillain-Barré syndrome (GBS) is an inflammatory disorder that may implicate proinflammatory cytokines such as tumor necrosis
factor alpha (TNF-alpha) in its pathogenesis. The association between TNF-alpha 308 G/A polymorphism and GBS largely remains
unknown. The aim of this study was to investigate the association between TNF-alpha 308 G/A polymorphism and GBS in Chinese
Han patients. TNF-alpha 308 G/A polymorphism in 150 GBS patients and 150 healthy controls were studied using polymerase chain
reaction–restriction fragment length polymorphism (PCR–RFLP) assay. Patients with GBS had a significantly higher frequency
of TNF-alpha 308AA genotype [odds ratio (OR) = 3.79, 95% confidence interval (CI) = 1.03, 13.94; P = 0.04] than controls. When stratified by the GBS subtype, there was a significantly higher frequency of TNF-alpha 308AA
genotype in patients with AMAN (OR = 6.05, 95% CI = 1.45, 25.31; P = 0.01) and AMSAN (OR = 5.56, 95% CI = 1.18, 26.23; P = 0.03) than controls. There was no significant difference in the distribution of each genotype between patients with AIDP
and the control group. These data indicated that TNF-alpha 308AA genotype was associated with a higher risk of GBS in Chinese
population, especially to AMAN and AMSAN. 相似文献
999.
Some studies have shown that IL-18 was associated with aetiology and progression of asthma. However, the association between
single-nucleotide polymorphisms −607C/A (rs1946518) and −137G/C (rs187238) located in the IL-18 gene promoter and asthma risk
was still controversial and ambiguous. To derive a more precise effect on the association between these polymorphisms and
asthma risk, we performed a meta-analysis based on the currently available evidence of the literature. A total of 5 studies
with 1411 cases and 1525 controls for −607C/A polymorphism and 5 studies with 1883 cases and 6645 controls for −137G/C polymorphism
were identified to perform a meta-analysis, up to October 2010. Summary ORs and corresponding 95% CIs for IL-18 polymorphisms
and asthma were estimated using fixed- and random-effects models when appropriate. Heterogeneity and publication bias were
evaluated. We found that individuals carrying AC/CC genotype of −607C/A polymorphism were associated with an increased asthma
risk in recessive model (OR = 1.278; 95% CI, 1.073–1.522). However, no significant association was observed between −137G/C
polymorphism and asthma risk under different contrast models. There was no evidence of publication bias. The present meta-analysis
suggested that IL-18 −607C/A polymorphism in promoter region was associated with asthma risk. 相似文献
1000.
To replicating the associations of type 2 diabetes (T2D) and six novel reported variants in Han Chinese lean individuals of
first episode T2D, a total of six high risk single nucleotide polymorphisms (SNPs) from the BCL11A, DUSP9, IRS1, CENTD2, ADRA2A, and CDKAL1 genes were examined. Candidate six SNPs were genotyped in 761 T2D patients and 433 control subjects, and associations between
the six SNPs and Body Mass Index (BMI), Fasting Plasma Glucose (FPG) and Two Hours Oral Glucose Tolerance Test (2hOGTT) were
also investigated. CDKAL1 provided the strongest evidence for replication, where rs7754840 was associated with T2D (odds ratio = 1.54, per copy of
the risk C allele, P = 8.10 × 10−7). SNP rs5945326 at DUSP9 showed modest significance (odds ratio = 0.81, per copy of the protective G allele, P = 0.02). After adjusting the confounders of age, gender and BMI, the above results remain significant for both rs7754840
(P < 1.0 × 10−4) and rs5945326 (P = 0.043) respectively. After correcting for multiple testing, however, only the association between T2D and rs7754840 at
CDKAL1 (P < 1×10−4) remains significant. In addition, the risk C allele of CDKAL1 rs7754840 was significantly associated with increased FPG levels (P = 3.8 × 10−4). The association between genetic variant in CDKAL1 gene was detected in the Han Chinese lean individuals. The correlation between rs7754840-C allele and increased FPG levels
is consistent with the potential function of CDKAL1 gene in pancreatic islets. 相似文献