全文获取类型
收费全文 | 21016篇 |
免费 | 1698篇 |
国内免费 | 1727篇 |
专业分类
24441篇 |
出版年
2024年 | 55篇 |
2023年 | 316篇 |
2022年 | 713篇 |
2021年 | 1155篇 |
2020年 | 767篇 |
2019年 | 977篇 |
2018年 | 918篇 |
2017年 | 618篇 |
2016年 | 912篇 |
2015年 | 1342篇 |
2014年 | 1520篇 |
2013年 | 1578篇 |
2012年 | 1935篇 |
2011年 | 1699篇 |
2010年 | 995篇 |
2009年 | 920篇 |
2008年 | 1088篇 |
2007年 | 904篇 |
2006年 | 827篇 |
2005年 | 649篇 |
2004年 | 508篇 |
2003年 | 448篇 |
2002年 | 374篇 |
2001年 | 324篇 |
2000年 | 321篇 |
1999年 | 324篇 |
1998年 | 208篇 |
1997年 | 242篇 |
1996年 | 191篇 |
1995年 | 189篇 |
1994年 | 162篇 |
1993年 | 129篇 |
1992年 | 181篇 |
1991年 | 143篇 |
1990年 | 146篇 |
1989年 | 98篇 |
1988年 | 90篇 |
1987年 | 87篇 |
1986年 | 63篇 |
1985年 | 65篇 |
1984年 | 43篇 |
1983年 | 47篇 |
1982年 | 21篇 |
1981年 | 16篇 |
1980年 | 14篇 |
1979年 | 12篇 |
1978年 | 10篇 |
1969年 | 9篇 |
1968年 | 8篇 |
1965年 | 16篇 |
排序方式: 共有10000条查询结果,搜索用时 39 毫秒
71.
In an F2 population of 120 plants derived from a cross between 2 breeding lines with yellow ray flowers, we observed 111 plants with yellow-colored and 9 plants with lemon-colored ray flowers. The segregation pattern fits a 15:1 (chi2(15:1) = 0.32, P > 0.5) ratio, suggesting that the lemon ray flower color is conditioned by 2 independent recessive genes that had been contributed individually by each of the parents. We sampled 111 plants from the 3 F(2:3) families displaying a 3 to 1 segregating ratio for genotyping with molecular markers. One of the genes, Yf(1), was mapped onto linkage group 11 of the public sunflower map. A targeted region amplified polymorphism marker (B26P17Trap13-68) had a genetic distance of 1.5 cM to Yf(1), and one simple sequence repeat marker (ORS733) and one expressed sequence tag (EST)-based marker (HT167) previously mapped to linkage group 11 were linked to Yf(1) with distances of 9.9 and 2.3 cM, respectively. 相似文献
72.
Focal adhesion kinase (FAK) functions as a key enzyme in the integrin-mediated adhesion-signalling pathway. Here, we aimed to investigate the effects of FAK on adhesion of human dental pulp (HDP) cells. We transfected lentiviral vectors to silence or overexpress FAK in HDP cells ex vivo. Early cell adhesion, cell survival and focal contacts (FCs)-related proteins (FAK and paxillin) were examined. By using immunofluorescence, the formation of FCs and cytoskeleton was detected, respectively. We found that both adhesion and survival of HDP cells were suppressed by FAK inhibition. However, FAK overexpression slightly inhibited cell adhesion and exhibited no change in cell survival compared with the control. A thick rim of cytoskeleton accumulated and smaller dot-shaped FCs appeared in FAK knockdown cells. Phosphorylation of paxillin (p-paxillin) was inhibited in FAK knockdown cells, verifying that the adhesion was inhibited. Less cytoskeleton and elongated FCs were observed in FAK-overexpressed cells. However, p-paxillin had no significant difference compared with the control. In conclusion, the data suggest that FAK maintains cell adhesion, survival and cytoskeleton formation, but excessive FAK has no positive effects on these aspects. 相似文献
73.
Li Wang Yun Xiao Yanyan Ping Jing Li Hongying Zhao Feng Li Jing Hu Hongyi Zhang Yulan Deng Jiawei Tian Xia Li 《PloS one》2014,9(8)
Cross-talk among abnormal pathways widely occurs in human cancer and generally leads to insensitivity to cancer treatment. Moreover, alterations in the abnormal pathways are not limited to single molecular level. Therefore, we proposed a strategy that integrates a large number of biological sources at multiple levels for systematic identification of cross-talk among risk pathways in cancer by random walk on protein interaction network. We applied the method to multi-Omics breast cancer data from The Cancer Genome Atlas (TCGA), including somatic mutation, DNA copy number, DNA methylation and gene expression profiles. We identified close cross-talk among many known cancer-related pathways with complex change patterns. Furthermore, we identified key genes (linkers) bridging these cross-talks and showed that these genes carried out consistent biological functions with the linked cross-talking pathways. Through identification of leader genes in each pathway, the architecture of cross-talking pathways was built. Notably, we observed that linkers cooperated with leaders to form the fundamentation of cross-talk of pathways which play core roles in deterioration of breast cancer. As an example, we observed that KRAS showed a direct connection to numerous cancer-related pathways, such as MAPK signaling pathway, suggesting that it may be a central communication hub. In summary, we offer an effective way to characterize complex cross-talk among disease pathways, which can be applied to other diseases and provide useful information for the treatment of cancer. 相似文献
74.
Kaidong Ma Hong Jin Rong Hu Yu Xiong Shufeng Zhou Peng Ting Yan Cheng Yan Yang Pengyuan Yang Xiaotian Li 《Cell biochemistry and biophysics》2014,69(2):247-258
To explore the proteomic changes of placental trophoblastic cells in preeclampsia–eclampsia (PE), placental trophoblastic cells from normally pregnant women and women with hypertension during gestational period were prepared by laser capture microdissection (LCM), and proteins isolated from these cells were subjected to labeling and proteolysis with isotope-coded affinity tag reagent. A qualitative and quantitative analysis of the proteome expression of placental trophoblastic cells was made using two-dimensional liquid chromatography tandem mass spectrometry (2D LC–MS/MS). A total of 831 proteins in placental trophoblastic cells were identified by combined use of LCM technique and 2D LC–MS/MS. The result was superior to that of conventional two-dimensional electrophoresis method. There were marked differences in 169 proteins of placental trophoblastic cells between normally pregnant women and women with PE. Of 70 (41.4 %) proteins with more than twofold differences, 31 proteins were down-regulated, and 39 were up-regulated in placental trophoblastic cells of the woman with PE. Laminin expression in placenta trophoblastic cells of women with PE was significantly down-regulated as confirmed by Western blot analysis. These findings provide insights into the proteomic changes in placental trophoblastic cells in response to PE and may identify novel protein targets associated with the pathogenesis of PE. 相似文献
75.
John C. Hu Camila Mathias-Santos Christopher J. Greene Natalie D. King-Lyons Juliana F. Rodrigues George Hajishengallis Luís C. S. Ferreira Terry D. Connell 《PloS one》2014,9(12)
Vaccinations are extremely effective at combating infectious diseases. Many conserved antigen (Ag) targets, however, are poorly immunogenic. Protein subunit vaccines frequently elicit only humoral immune responses and fail to confer protection against serious intracellular pathogens. These barriers to vaccine development are often overcome by the use of appropriate adjuvants. Heat-labile enterotoxins (HLT) produced by enterotoxigenic strains of Escherichia coli are potent adjuvants when administered by mucosal or systemic routes. The efficacy of the type II HLT, however, has not been well-defined when administered by the intradermal (ID) route. Using a murine ID immunization model, the adjuvant properties of LT-IIb and LT-IIc, two type II HLTs, were compared with those of LT-I, a prototypical type I HLT. While all three HLT adjuvants enhanced Ag-specific humoral responses to similar levels, LT-IIb and LT-IIc, in contrast to LT-I, induced a more vigorous Ag-specific CD8+ T cell response and proffered faster clearance of Listeria monocytogenes in a challenge model. Additionally, LT-IIb and LT-IIc induced distinct differences in the profiles of the Ag-specific CD8+ T cell responses. While LT-IIc stimulated a robust and rapid primary CD8+ T cell response, LT-IIb exhibited slower CD8+ T cell expansion and contraction kinetics with the formation of higher percentages of effector memory cells. In comparison to LT-I and LT-IIc, LT-IIb evoked better long-term protection after immunization. Furthermore, LT-IIb and LT-IIc enhanced the total number of dendritic cells (DC) in the draining lymph node (DLN) and expression of costimulatory molecules CD80, CD86, and CD40 on DCs. In contrast to LT-I, LT-IIb and LT-IIc induced less edema, cellular infiltrates, and general inflammation at the site of ID injection. Thus, LT-IIb and LT-IIc are attractive comprehensive ID adjuvants with unique characteristic that enhance humoral and cellular immunity to a co-administered protein Ag. 相似文献
76.
77.
78.
The development of novel targeted therapies holds promise for conquering chemotherapy resistance, which is one of the major hurdles in current breast cancer treatment. Previous studies indicate that mitochondria uncoupling protein 2 (UCP-2) is involved in the development of chemotherapy resistance in colon cancer and lung cancer cells. In the present study we found that lower level of miR133a is accompanied by increased expression of UCP-2 in Doxorubicin-resistant breast cancer cell cline MCF-7/Dox as compared with its parental cell line MCF-7. We postulated that miR133a might play a functional role in the development of Doxorubicin-resistant in breast cancer cells. In this study we showed that: 1) exogenous expression of miR133a in MCF-7/Dox cells can sensitize their reaction to the treatment of Doxorubicin, which is coincided with reduced expression of UCP-2; 2) knockdown of UCP-2 in MCF-7/Dox cells can also sensitize their reaction to the treatment of Doxorubicin; 3) intratumoral delivering of miR133a can restore Doxorubicin treatment response in Doxorubicin-resistant xenografts in vivo, which is concomitant with the decreased expression of UCP-2. These findings provided direct evidences that the miR133a/UCP-2 axis might play an essential role in the development of Doxorubicin-resistance in breast cancer cells, suggesting that the miR133a/UCP-2 signaling cohort could be served as a novel therapeutic target for the treatment of chemotherapy resistant in breast cancer. 相似文献
79.
80.
Gui-qiang Liu Zheng-qi Liu Kuan Huang Yuan-hao Chen Zheng-jie Cai Xiang-nan Zhang Ying Hu 《Plasmonics (Norwell, Mass.)》2014,9(1):17-25
We study the cooperative effects between plasmon gap modes and optical cavity modes of a novel triple-layer structure consisting of double continuous gold films separated by a gold nanosphere array. Narrowband near-perfect antireflection of optical field is achieved for the first time due to the strong near-field light–matter interaction within the deep sub-wavelength gaps between adjacent nanospheres combined with the spatial field confinement effects of the optical cavity built by the double gold films. The coexistence cooperation of near-field dipole plasmon resonances and spatial optical field confinement presents more efficient light modification than that of the individual subsystem and may open a new approach to manage light flow. By varying the period of nanosphere array, the diameter of nanospheres, and the distance between the array and the film, optical behaviors of the proposed structure can be tuned in a wide range. High environmental sensitivity and large figure of merit factor are obtained using this structure as the detecting substrate. Furthermore, ultra-compact structure and high conduction suggest the proposed structure being a good candidate for potential applications in highly integrated optoelectronic devices, such as plasmonic filters and sensors. 相似文献