全文获取类型
收费全文 | 11413篇 |
免费 | 456篇 |
国内免费 | 74篇 |
专业分类
化学 | 7843篇 |
晶体学 | 133篇 |
力学 | 341篇 |
数学 | 958篇 |
物理学 | 2668篇 |
出版年
2023年 | 72篇 |
2022年 | 239篇 |
2021年 | 276篇 |
2020年 | 223篇 |
2019年 | 222篇 |
2018年 | 215篇 |
2017年 | 180篇 |
2016年 | 357篇 |
2015年 | 340篇 |
2014年 | 441篇 |
2013年 | 736篇 |
2012年 | 903篇 |
2011年 | 1031篇 |
2010年 | 564篇 |
2009年 | 504篇 |
2008年 | 759篇 |
2007年 | 705篇 |
2006年 | 635篇 |
2005年 | 601篇 |
2004年 | 493篇 |
2003年 | 389篇 |
2002年 | 387篇 |
2001年 | 248篇 |
2000年 | 216篇 |
1999年 | 153篇 |
1998年 | 86篇 |
1997年 | 93篇 |
1996年 | 107篇 |
1995年 | 95篇 |
1994年 | 88篇 |
1993年 | 66篇 |
1992年 | 68篇 |
1991年 | 59篇 |
1990年 | 61篇 |
1989年 | 38篇 |
1988年 | 31篇 |
1987年 | 15篇 |
1986年 | 12篇 |
1985年 | 26篇 |
1984年 | 18篇 |
1983年 | 17篇 |
1982年 | 19篇 |
1981年 | 16篇 |
1980年 | 12篇 |
1979年 | 13篇 |
1978年 | 16篇 |
1977年 | 10篇 |
1976年 | 13篇 |
1975年 | 10篇 |
1972年 | 9篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
961.
Jong Young Joung Ha Yeon Lee Jongil Park Jee-Young Lee Byung Ha Chang Kyoung Tai No Ky-Youb Nam Jae Sung Hwang 《Applied biochemistry and biotechnology》2014,172(4):1882-1897
Melanocytes are unique cells that produce specific melanin-containing intracellular organelles called melanosomes. Melanosomes are transported from the perinuclear area of melanocytes toward the plasma membrane as they become more melanized in order to increase skin pigmentation. In this vesicular trafficking of melanosomes, Rab27a, melanophilin, and myosin Va play crucial roles in linking melanosomes to actin-based motors. To identify novel compounds to inhibit binding interface between Rab27a and melanophilin, a pharmacophore model was built based on a modeled 3D structure of the protein complex that describes the essential binding residues in the intermolecular interaction. A pharmacophore model was employed to screen a chemical library database. Finally, 25 virtual hits were selected for biological evaluations. The biological activities of 11 analogues were evaluated in a second assay. Two compounds were identified as having concentration-dependent inhibitory activity. By analyzing structure–activity relationships of derivatives of BMD-20, two hydroxyl functional groups were found to be critical for blocking the intermolecular binding between Rab27a and melanophilin. 相似文献
962.
963.
Jong Eel Park Kyeong Wan Woo Sang Un Choi Je Hyun Lee Kang Ro Lee 《Helvetica chimica acta》2014,97(1):56-63
Two new spirostane‐steroidal saponins, bletilnoside A ( 1 ) and bletilnoside B ( 2 ), together with five known compounds, 3 – 7 , were isolated from the roots of Bletilla striata (Thunb .) Reichb . F. The structures of the new compounds were determined based on their 1D‐ and 2D‐NMR spectral data. The isolated compounds 1 – 7 were tested for cytotoxicity against four human tumor cells (A549, SK‐OV‐3, SK‐MEL‐2, and HCT15) in vitro using a sulforhodamin B bioassay, and compounds 1, 2 , and 5 showed significant cytotoxicities against all tested tumor cell lines with IC50 values ranging from 3.98±0.16 to 12.10±0.40 μM . 相似文献
964.
Dongjoon Lee Jong-Chan Park Keum Sim Jung Jiyeong Kim Ji Sung Jang Sunghoon Kwon Min Soo Byun Dahyun Yi Gihwan Byeon Gijung Jung Yu Kyeong Kim Dong Young Lee Sun-Ho Han Inhee Mook-Jung 《Experimental & molecular medicine》2022,54(1):61
The deposition of beta-amyloid (Aβ) in the brain precedes the onset of symptoms such as cognitive impairment in Alzheimer’s disease (AD); therefore, the early detection of Aβ accumulation is crucial. We previously reported the applicability of the QPLEXTM Alz plus assay kit for the prescreening of Aβ accumulation. Here, we tested the specific application of the kit in a large cohort of cognitively normal (CN) individuals of varying ages for the early detection of Aβ accumulation. We included a total of 221 CN participants with or without brain Aβ. The QPLEXTM biomarkers were characterized based on age groups (1st–3rd tertile) and across various brain regions with cerebral amyloid deposition. The 3rd tertile group (>65 years) was found to be the most suitable age group for the application of our assay kit. Receiver operating characteristic curve analysis showed that the area under the curve (AUC, discrimination power) was 0.878 with 69.7% sensitivity and 98.4% specificity in the 3rd tertile group. Additionally, specific correlations between biomarkers and cerebral amyloid deposition in four different brain regions revealed an overall correlation with general amyloid deposition, consistent with previous findings. Furthermore, the combinational panel with plasma Aβ1–42 levels maximized the discrimination efficiency and achieved an AUC of 0.921 with 95.7% sensitivity and 67.3% specificity. Thus, we suggest that the QPLEXTM Alz plus assay is useful for prescreening brain Aβ levels in CN individuals, especially those aged >65 years, to prevent disease progression via the early detection of disease initiation.Subject terms: Alzheimer''s disease, Neural ageing, ELISA 相似文献
965.
Leukocyte adhesion to the endothelium through surface molecules such as E-selectin and intercellular adhesion molecule-1 (ICAM-1) is a critical cellular event reflecting the physiological status of both cell types. Here we present a microfluidic system that can not only easily monitor the interaction between leukocytes and endothelial cells under physiological conditions, but also screen drug candidates for potential modulation of this interaction. Shear stress, which is an important factor for the binding of activated T cells to tumor necrosis factor-alpha (TNF-α)-treated human umbilical vein endothelial cells (HUVECs), was easily controlled by adjusting the flow rate in the microfluidic system. Whole blood of patients with systemic lupus erythematosus (SLE) who have auto-reactive T cells were infused into the activated HUVECs which subsequently showed a higher level of binding compared to a control blood sample from a person without SLE. When these autoreactive T cells were treated with immunosuppressors tacrolimus and cyclosporin A, the binding of the T cells to HUVECs was dramatically decreased. Therefore, this microfluidic system is capable of differentiating the physiological status of T cells or endothelial cells representing different disease conditions, as well as being useful for the identification of novel reagents that modulate the functions of leukocytes or endothelial cells. 相似文献
966.
The preparation of an 1,3-alternate calix[4]arene phosphorus ligand, 25,27-bis(2-(diphenylphosphino)ethoxy)-26,28-bis(1-propyloxy)calix[4]arene (3), is presented. Ligand 3 is obtained in three steps in 64% overall yield. Reaction of 3 with [Rh(cot)2]BF4 produced the encapsulated rhodium complex [Rh[(P,P)-diphen-calix[4]arene]]BF4 (4). As revealed by a single-crystal X-ray diffraction study, the rhodium center has a bent coordination environment with a P-Rh-P angle of 135.66(3) degrees. Palladation of 3 employing [Pd(MeCN)4](BF4)2 yielded the chelate palladium complex 7 in which the palladium center has a slightly bent configuration. Treatment of the ligand with Pd(cod)Cl2 and [Pd(eta3-C4H7)(THF)2]BF4 leads to the isolation of the monometallic complex. Full characterization includes X-ray structural studies of compounds 3, 4, and 6. 相似文献
967.
The radical addition reactions of α-substituted β,β-difluorovinyl sulfones 1 with α-oxy and acyl radical species, such as 1,3-dioxolane, tetrahydrofuran, 1,4-dioxane, butanal and hexanal, afforded radical addition products 2--16 in good yields. 相似文献
968.
969.
We describe an accurate method for protein quantification based on conventional acid hydrolysis and an isotope dilution-HPLC-mass spectrometry (ID-HPLC-MS) method. Sample purity was confirmed using capillary zone electrophoresis, HPLC and MS. The analyte protein, human growth hormone (hGH), was effectively hydrolyzed by incubation with 8 M hydrochloric acid at 130 °C for 48 h, where at least 1 μM of hGH was treated to avoid possible degradation of released amino acids during hydrolysis. Using a reversed-phase column, the analytes (isoleucine, phenylalanine, proline and valine) were separated within 5 min using an isocratic eluent comprising 10% acetonitrile containing 0.1% trifluoroacetic acid. The detection limit (signal to noise ratio of 3) of amino acids was 5.5-6.2 fmol per injection. The quantification precision (RSD) of amino acids for intra- and inter-day assays was less than 0.98% and 0.39%, respectively. Comparison with other biochemical and instrumental methods revealed substantially higher accuracy and reproducibility of the ID-HPLC-MS/MS method as expected. The optimized hydrolysis and analytical conditions in our study were suitable for accurate quantification of hGH. 相似文献
970.
Oh BN Park S Ren J Jang YJ Kim SK Kim J 《Dalton transactions (Cambridge, England : 2003)》2011,40(24):6494-6499
In this study, an assay to quantify the presence of mercuric ions and methyl mercury by double-stranded DNA containing a poly(dT) sequence was developed using a light switch compound, Ru(phen)(2)(dppz)(2+) (1), which is known to intercalate into double-stranded DNA. Upon treatment with mercuric ions, the metal-to-ligand charge transfer (MLCT) emission derived from the intercalation of 1 was reduced due to the formation of DNA duplexes containing T-Hg(2+)-T base pairs by the dehybridization of poly(dT)-poly(dA) duplexes at room temperature. As the concentration of Hg(2+) was increased, the emission of 1 gradually decreased. This label-free method had a detection limit of 5 nM. Other metal ions, such as K(+), Ag(+), Ca(2+), Mg(2+), Zn(2+), Mn(2+), Co(2+), Ni(2+), Cu(2+), Cd(2+), Cr(3+), Fe(3+), had no significant effect on reducing emission. This emission method can differentiate matched and mismatched poly(dT) sequences based on the dehybridization rate of dsDNA and the rate decreased in the order of T(10)C·A(11)~ T(10)A·A(11) > T(10)G·A(11) > T(11)·A(11). 相似文献