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51.
52.
Won Gi Yoo Sanghyun Lee Myoung-Ro Lee Mi-Ran Yun Taesoo Kwon Dae-Won Kim 《Bioinformation》2015,11(1):17-20
The increase in prevalence of antimicrobial resistance makes the search for new antibiotic agents imperative. Antimicrobial
peptides (AMPs) from natural resources have been recognized as suitable tools to combat antibiotic-resistant bacteria. The liver
fluke Clonorchis sinensis living in germ-filled environments could be a good source of antimicrobials. Here, we report the use of a
rational protocol that combines AMP predictions based on their physicochemical properties and their in vivo stability to discover
AMP candidates from the entire genome of C. sinensis. To screen AMP candidates, in silico analyses based on the physicochemical
properties of known AMPs, such as length, charge, isoelectric point, and in vitro and in vivo aggregation values were performed. To
enhance their in vivo stability, proteins having proteolytic cleavage sites were excluded. As a consequence, four high-activity, highstability
peptides were identified. These peptides could be potential starting materials for the development of new AMPs via
structural modification and optimization. Thus, this study proposes a refined computational method to develop new AMPs and
identifies four AMP candidates, which could serve as templates for further development of peptide antibiotics. 相似文献
53.
Dong Hyun Sinn Ju-Yeon Cho Geum-Youn Gwak Yong-Han Paik Moon Seok Choi Joon Hyeok Lee Kwang Cheol Koh Seung Woon Paik Byung Chul Yoo 《PloS one》2015,10(4)
Portal vein invasion (PVI) and extrahepatic spread (ES) are two tumor-related factors that define advanced stage in the Barcelona Clinic Liver Cancer (BCLC) staging system (BCLC stage C), and the recommended first line therapy in this stage is sorafenib. However, the extent of PVI and the type of ES may affect patient prognosis as well as treatment outcome. This study analyzed survival of BCLC stage C HCC patients in order to see whether sub-classification of BCLC stage C is necessary. A total of 582 treatment naïve, BCLC stage C HCC patients [age: 54.3 ± 10.8 years, males = 494 (84.9%), hepatitis B virus (458, 78.7%)], defined by PVI and/or ES, were analyzed. Extent of PVI was divided into none, type I-segmental/sectoral branches, type II-left and/or right portal vein, and type III-main portal vein trunk. Type of ES was divided into nodal and distant metastasis. The extent of PVI and type of ES were independent factors for survival. When patients were sub-classified according to the extent of PVI and type of ES, the median survival was significantly different [11.7 months, 5.7 months, 4.9 months and 2.3 months for C1 (PVI-O/I without distant ES), C2 (PVI-II/III without distant ES), C3 (PVI-0/I with distant ES), and C4 (PVI-II/III with distant ES), respectively, P = 0.01]. Patients’ survival was different according to the treatment modality in each sub-stage. Sub-classification of BCLC stage C according to the extent of PVI and type of ES resulted in a better prediction of survival. Also, different outcome was observed by treatment modalities in each sub-stage. Sub-classification of BCLC stage C is required to minimize heterogeneity within the same tumor stage, that will help better predict survival and to select optimal treatment strategies. 相似文献
54.
Kwangsun Yoo Sun Ju Chung Ho Sung Kim Oh-hyeon Choung Young-Beom Lee Mi-Jung Kim Sooyeoun You Yong Jeong 《PloS one》2015,10(4)
Background
Recently, non-motor symptoms of Parkinson’s disease (PD) have been considered crucial factors in determining a patient’s quality of life and have been proposed as the predominant features of the premotor phase. Researchers have investigated the relationship between non-motor symptoms and the motor laterality; however, this relationship remains disputed. This study investigated the neural connectivity correlates of non-motor and motor symptoms of PD with respect to motor laterality.Methods
Eight-seven patients with PD were recruited and classified into left-more-affected PD (n = 44) and right-more affected PD (n = 37) based on their MDS-UPDRS (Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale) motor examination scores. The patients underwent MRI scanning, which included resting fMRI. Brain regions were labeled as ipsilateral and contralateral to the more-affected body side. Correlation analysis between the functional connectivity across brain regions and the scores of various symptoms was performed to identify the neural connectivity correlates of each symptom.Results
The resting functional connectivity centered on the ipsilateral inferior orbito-frontal area was negatively correlated with the severity of non-motor symptoms, and the connectivity of the contralateral inferior parietal area was positively correlated with the severity of motor symptoms (p < 0.001, |r| > 0.3).Conclusions
These results suggest that the inferior orbito-frontal area may play a crucial role in non-motor dysfunctions, and that the connectivity information may be utilized as a neuroimaging biomarker for the early diagnosis of PD. 相似文献55.
Eun Ju Cho Jeong-Hoon Lee Yuri Cho Yun Bin Lee Jeong-Ju Yoo Minjong Lee Dong Hyeon Lee Su Jong Yu Yoon Jun Kim Jung-Hwan Yoon Hyo-Suk Lee 《PloS one》2015,10(6)
The efficacy of entecavir (ETV) and tenofovir (TDF) for the treatment of nucleos(t)ide analogue (NA)-experienced chronic hepatitis B (CHB) patients has been little studied. Here, we compare the efficacy of both ETV and TDF in NA-experienced CHB patients without detectable genotypic resistance. This retrospective cohort study included consecutive NA-experienced patients who had neither current nor previous genotypic resistance and had received ETV or TDF for at least 6 months. Overall, 202 patients (146 patients in the ETV group and 56 in the TDF group) were analyzed. The cumulative probabilities of complete virologic suppression (CVS) at month 12 were 76.1% in the ETV group and 95.0% in the TDF group (P<0.001), respectively. The TDF-treated group achieved CVS more rapidly than the ETV group for both Hepatitis B e antigen (HBeAg)-negative and -positive patients (P = 0.006 and < 0.001, respectively), and for those with both low (< 2,000 IU/mL) and high (≥ 2,000 IU/mL) HBV DNA levels (P = 0.01 and 0.002, respectively). TDF group had an increased probability of achieving CVS (hazard ratio, 2.242; 95% confidence interval, 1.587–3.165; P = 0.001), after adjustment for HBV DNA level, the presence of HBeAg, and a history of CVS during prior treatment. During the treatment period, 23 patients (15.8%) in the ETV group developed virologic breakthrough, compared to none in the TDF group. The cumulative probabilities of developing virologic breakthrough and ETV-resistance at month 24 were 9.7% and 5.3%, respectively. In conclusion, TDF is preferable to ETV for achieving CVS in NA-experienced CHB patients without genotypic resistance. 相似文献
56.
Dong Kyung Sung Yun Sil Chang So Yoon Ahn Se In Sung Hye Soo Yoo Soo Jin Choi Soo Yoon Kim Won Soon Park 《PloS one》2015,10(8)
The aim of this study was to determine the optimal route of mesenchymal stem cell (MSC) transplantation. To this end, gene expression profiling was performed to compare the effects of intratracheal (IT) versus intravenous (IV) MSC administration. Furthermore, the therapeutic efficacy of each route to protect against neonatal hyperoxic lung injury was also determined. Newborn Sprague-Dawley rats were exposed to hyperoxia (90% oxygen) from birth for 14 days. Human umbilical cord blood-derived MSCs labeling with PKH26 were transplanted through either the IT (5×105) or IV (2×106) route at postnatal day (P) 5. At P14, lungs were harvested for histological, biochemical and microarray analyses. Hyperoxic conditions induced an increase in the mean linear intercept and mean alveolar volume (MAV), indicative of impaired alveolarization. The number of ED-1 positive cells was significantly decreased by both IT and IV transplantations. However, IT administration of MSCs resulted in a greater decrease in MAV and ED-1 positive cells compared to IV administration. Moreover, the number of TUNEL-positive cells was significantly decreased in the IT group, but not in the IV group. Although the IT group received only one fourth of the number of MSCs that the IV group did, a significantly higher number of donor cell-derived red PKH 26 positivity were recovered in the IT group. Hyperoxic conditions induced the up regulation of genes associated with the inflammatory response, such as macrophage inflammatory protein-1 α, tumor necrosis factor-α and inter leukin-6; genes associated with cell death, such as p53 and caspases; and genes associated with fibrosis, such as connective tissue growth factor. In contrast, hyperoxic conditions induced the dwon-regulation of vascular endothelial growth factor and hepatocyte growth factor. These hyperoxia-induced changes in gene expression were decreased in the IT group, but not in the IV group. Thus, local IT MSC transplantation was more effective than systemic IV MSC administration in protecting against neonatal hyperoxic lung injury. 相似文献
57.
Dong Geon Kim Younggeon Jin Juyoun Jin Heekyoung Yang Kyeung Min Joo Weon Sup Lee Sang Ryeol Shim Sung-Woo Kim Jinsang Yoo Sang Hoon Lee Jin-San Yoo Do-Hyun Nam 《MABS-AUSTIN》2015,7(6):1195-1204
Vascular endothelial growth factor (VEGF) and its receptors are considered the primary cause of tumor-induced angiogenesis. Specifically, VEGFR-2/kinase insert domain receptor (KDR) is part of the major signaling pathway that plays a significant role in tumor angiogenesis, which is associated with the development of various types of tumor and metastasis. In particular, KDR is involved in tumor angiogenesis as well as cancer cell growth and survival. In this study, we evaluated the therapeutic potential of TTAC-0001, a fully human antibody against VEGFR-2/KDR. To assess the efficacy of the antibody and pharmacokinetic (PK) relationship in vivo, we tested the potency of TTAC-0001 in glioblastoma and colorectal cancer xenograft models. Antitumor activity of TTAC-0001 in preclinical models correlated with tumor growth arrest, induction of tumor cell apoptosis, and inhibition of angiogenesis. We also evaluated the combination effect of TTAC-0001 with a chemotherapeutic agent in xenograft models. We were able to determine the relationship between PK and the efficacy of TTAC-0001 through in vivo single-dose PK study. Taken together, our data suggest that targeting VEGFR-2 with TTAC-0001 could be a promising approach for cancer treatment. 相似文献
58.
Colorectal cancer (CRC), the third most common cancer worldwide, also has the
highest rate of cancer-related morbidity and mortality. WNT signaling is
initiated by binding of WNT to various receptors, including frizzleds (FZDs),
and plays a critical role in CRC and other tumor development by regulating
proliferation, differentiation, migration, apoptosis, and polarity. Among the
members of the FZD family, FZD6 is broadly expressed in various tissues, and its
overexpression has been reported in several cancers, suggesting an important
role in cancer development. In this study, we investigated the expression of
FZD6 in patients with CRC and found it to be increased in tumors, as compared to
paired adjacent non-tumor tissues. Additionally, we found that FZD6 expression
was negatively regulated by miR199a5p in CRC cells. These results suggest that
overexpression of FZD6, mediated by reduced expression of miR-199a-5p, may play
an important role in the development of CRC. [BMB Reports 2015; 48(6):
360-366] 相似文献
59.
Yoo Jung Park Ha Young Lee Young Su Jung Joon Seong Park Jae Sam Hwang Yoe-Sik Bae 《BMB reports》2015,48(8):479-484
In this study, we report that one of the antimicrobial peptides scolopendrasin VII, derived from Scolopendra subspinipes mutilans, stimulates actin polymerization and the subsequent chemotactic migration of macrophages through the activation of ERK and protein kinase B (Akt) activity. The scolopendrasin VII-induced chemotactic migration of macrophages is inhibited by the formyl peptide receptor 1 (FPR1) antagonist cyclosporine H. We also found that scolopendrasin VII stimulate the chemotactic migration of FPR1-transfected RBL-2H3 cells, but not that of vector-transfected cells; moreover, scolopendrasin VII directly binds to FPR1. Our findings therefore suggest that the antimicrobial peptide scolopendrasin VII, derived from Scolopendra subspinipes mutilans, stimulates macrophages, resulting in chemotactic migration via FPR1 signaling, and the peptide can be useful in the study of FPR1-related biological responses. [BMB Reports 2015; 48(8): 479-484] 相似文献
60.