全文获取类型
收费全文 | 4076篇 |
免费 | 308篇 |
国内免费 | 2篇 |
出版年
2023年 | 18篇 |
2021年 | 103篇 |
2020年 | 51篇 |
2019年 | 75篇 |
2018年 | 74篇 |
2017年 | 72篇 |
2016年 | 112篇 |
2015年 | 186篇 |
2014年 | 209篇 |
2013年 | 263篇 |
2012年 | 323篇 |
2011年 | 272篇 |
2010年 | 168篇 |
2009年 | 138篇 |
2008年 | 197篇 |
2007年 | 172篇 |
2006年 | 183篇 |
2005年 | 159篇 |
2004年 | 154篇 |
2003年 | 138篇 |
2002年 | 136篇 |
2001年 | 106篇 |
2000年 | 89篇 |
1999年 | 81篇 |
1998年 | 40篇 |
1997年 | 33篇 |
1996年 | 16篇 |
1995年 | 29篇 |
1994年 | 40篇 |
1993年 | 25篇 |
1992年 | 52篇 |
1991年 | 55篇 |
1990年 | 56篇 |
1989年 | 42篇 |
1988年 | 47篇 |
1987年 | 30篇 |
1986年 | 26篇 |
1985年 | 46篇 |
1984年 | 35篇 |
1983年 | 29篇 |
1982年 | 17篇 |
1979年 | 25篇 |
1978年 | 24篇 |
1977年 | 20篇 |
1975年 | 22篇 |
1974年 | 23篇 |
1973年 | 15篇 |
1971年 | 24篇 |
1970年 | 16篇 |
1969年 | 17篇 |
排序方式: 共有4386条查询结果,搜索用时 165 毫秒
1.
Sven Skog Viola Eriksson Eva Eliasson 《Biochimica et Biophysica Acta (BBA)/General Subjects》1981,672(1):33-44
Suspension cultures of ‘Chang liver’ cells were synchronized by preincubation in a glutamine-deficient medium or by thymidine blockade. Specific arginase activity varied in the synchronized cultures, being high when the number of S-phase cells was maximal. A relationship between high arginase activity and a high percentage of (S+G2) cells was also found when unsynchronized cells were separated by velocity sedimentation. The increase in arginase activity near the G1/S border was totally inhibited in the presence of cycloheximide. The rate of decrease in activity after addition of the drug indicated that the variations in the rate of synthesis of the enzyme, while the rate of degradation was more or less constant, corresponding to 4–6% per h. The role of arginase in cells lacking a urea cycle and the regulation of arginase activity in ‘Chang liver’ cells is discussed. 相似文献
2.
Recent studies have shown that cells expressing neuronal antigens can be derived from a bone marrow transplant. A new report lends support to and extends these previous results by presenting compelling morphological evidence for the generation and integration of highly differentiated bone marrow-derived neurons. 相似文献
3.
Hanna Gladh Erika Bergsten Folestad Lars Muhl Monika Ehnman Philip Tannenberg Anna-Lisa Lawrence Christer Betsholtz Ulf Eriksson 《PloS one》2016,11(3)
Platelet-derived growth factor D (PDGF-D) is the most recently discovered member of the PDGF family. PDGF-D signals through PDGF receptor β, but its biological role remains largely unknown. In contrast to other members of the PDGF family of growth factors, which have been extensively investigated using different knockout approaches in mice, PDGF-D has until now not been characterized by gene inactivation in mice. Here, we present the phenotype of a constitutive Pdgfd knockout mouse model (Pdgfd-/-), carrying a LacZ reporter used to visualize Pdgfd promoter activity. Inactivation of the Pdgfd gene resulted in a mild phenotype in C57BL/6 mice, and the offspring was viable, fertile and generally in good health. We show that Pdgfd reporter gene activity was consistently localized to vascular structures in both postnatal and adult tissues. The expression was predominantly arterial, often localizing to vascular bifurcations. Endothelial cells appeared to be the dominating source for Pdgfd, but reporter gene activity was occasionally also found in subpopulations of mural cells. Tissue-specific analyses of vascular structures revealed that NG2-expressing pericytes of the cardiac vasculature were disorganized in Pdgfd-/- mice. Furthermore, Pdgfd-/- mice also had a slightly elevated blood pressure. In summary, the vascular expression pattern together with morphological changes in NG2-expressing cells, and the increase in blood pressure, support a function for PDGF-D in regulating systemic arterial blood pressure, and suggests a role in maintaining vascular homeostasis. 相似文献
4.
Chung-Te Chang Natalia Bercovich Belinda Loh Stefanie Jonas Elisa Izaurralde 《Nucleic acids research》2014,42(8):5217-5233
The removal of the 5′-cap structure by the decapping enzyme DCP2 and its coactivator DCP1 shuts down translation and exposes the mRNA to 5′-to-3′ exonucleolytic degradation by XRN1. Although yeast DCP1 and DCP2 directly interact, an additional factor, EDC4, promotes DCP1–DCP2 association in metazoan. Here, we elucidate how the human proteins interact to assemble an active decapping complex and how decapped mRNAs are handed over to XRN1. We show that EDC4 serves as a scaffold for complex assembly, providing binding sites for DCP1, DCP2 and XRN1. DCP2 and XRN1 bind simultaneously to the EDC4 C-terminal domain through short linear motifs (SLiMs). Additionally, DCP1 and DCP2 form direct but weak interactions that are facilitated by EDC4. Mutational and functional studies indicate that the docking of DCP1 and DCP2 on the EDC4 scaffold is a critical step for mRNA decapping in vivo. They also revealed a crucial role for a conserved asparagine–arginine containing loop (the NR-loop) in the DCP1 EVH1 domain in DCP2 activation. Our data indicate that DCP2 activation by DCP1 occurs preferentially on the EDC4 scaffold, which may serve to couple DCP2 activation by DCP1 with 5′-to-3′ mRNA degradation by XRN1 in human cells. 相似文献
5.
John A. Nyakatura Vivian R. Allen Jonas Laustr?er Amir Andikfar Marek Danczak Hans-Jürgen Ullrich Werner Hufenbach Thomas Martens Martin S. Fischer 《PloS one》2015,10(9)
Orobates pabsti, a basal diadectid from the lower Permian, is a key fossil for the understanding of early amniote evolution. Quantitative analysis of anatomical information suffers from fragmentation of fossil bones, plastic deformation due to diagenetic processes and fragile preservation within surrounding rock matrix, preventing further biomechanical investigation. Here we describe the steps taken to digitally reconstruct MNG 10181, the holotype specimen of Orobates pabsti, and subsequently use the digital reconstruction to assess body mass, position of the centre of mass in individual segments as well as the whole animal, and study joint mobility in the shoulder and hip joints. The shape of most fossil bone fragments could be recovered from micro-focus computed tomography scans. This also revealed structures that were hitherto hidden within the rock matrix. However, parts of the axial skeleton had to be modelled using relevant isolated bones from the same locality as templates. Based on the digital fossil, mass of MNG 10181 was estimated using a model of body shape that was varied within a plausible range to account for uncertainties of the dimension. In the mean estimate model the specimen had an estimated mass of circa 4 kg. Varying of the mass distribution amongst body segments further revealed that Orobates carried most of its weight on the hind limbs. Mostly unrestricted joint morphology further suggested that MNG 10181 was able to effectively generate propulsion with the pelvic limbs. The digital reconstruction is made available for future biomechanical studies. 相似文献
6.
Michaela Ludolphs Daniela Schneeberger Tolga Soykan Jonas Sch?fer Theofilos Papadopoulos Nils Brose Hermann Schindelin Claudia Steinem 《The Journal of biological chemistry》2016,291(1):244-254
The regulatory protein collybistin (CB) recruits the receptor-scaffolding protein gephyrin to mammalian inhibitory glycinergic and GABAergic postsynaptic membranes in nerve cells. CB is tethered to the membrane via phosphoinositides. We developed an in vitro assay based on solid-supported 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine membranes doped with different phosphoinositides on silicon/silicon dioxide substrates to quantify the binding of various CB2 constructs using reflectometric interference spectroscopy. Based on adsorption isotherms, we obtained dissociation constants and binding capacities of the membranes. Our results show that full-length CB2 harboring the N-terminal Src homology 3 (SH3) domain (CB2SH3+) adopts a closed and autoinhibited conformation that largely prevents membrane binding. This autoinhibition is relieved upon introduction of the W24A/E262A mutation, which conformationally “opens” CB2SH3+ and allows the pleckstrin homology domain to properly bind lipids depending on the phosphoinositide species with a preference for phosphatidylinositol 3-monophosphate and phosphatidylinositol 4-monophosphate. This type of membrane tethering under the control of the release of the SH3 domain of CB is essential for regulating gephyrin clustering. 相似文献
7.
Jonas G. Barlind Linda K. Buckett Sharon G. Crosby Öjvind Davidsson Hans Emtenäs Anne Ertan Ulrik Jurva Malin Lemurell Pablo Morentin Gutierrez Karolina Nilsson Gavin O’Mahony Annika U. Petersson Alma Redzic Fredrik Wågberg Zhong-Qing Yuan 《Bioorganic & medicinal chemistry letters》2013,23(9):2721-2726
[Acyl CoA]monoacylglycerol acyltransferase 2 (MGAT2) is of interest as a target for therapeutic treatment of diabetes, obesity and other diseases which together constitute the metabolic syndrome. In this Letter we report our discovery and optimisation of a novel series of MGAT2 inhibitors. The development of the SAR of the series and a detailed discussion around some key parameters monitored and addressed during the lead generation phase will be given. The in vivo results from an oral lipid tolerance test (OLTT) using the MGAT2 inhibitor (S)-10, shows a significant reduction (68% inhibition relative to na?ve, p <0.01) in plasma triacylglycerol (TAG) concentration. 相似文献
8.
9.
C J Eriksson 《Mutation research》1987,186(3):235-240
The determination of acetaldehyde levels in blood and other tissues is a difficult task, and depends on the method used. Different methods and their pros and cons are discussed in detail. Quantitative results are shown for endogenous acetaldehyde levels and for acetaldehyde levels during alcohol intoxication. One article pertains to acetaldehyde bound to blood and tissue proteins. 相似文献
10.
Twelve pig buttock island flaps (10 X 10 cm) were studied for 6 hours after arteriovenous flow reversal at the level of the pedicle. Follow-up was 48 hours. Blood pressure, Po2, pH, and lactate were measured in flap arteries and veins. Oxygen consumption was calculated. Data indicated true flow reversal. Blood pressure and Po2 in flap veins increased to systemic arterial levels. Outflow was provided by the arterial system, demonstrating venous pressure and Po2 values. Lactate increased significantly (1.8 +/- 0.5 to 4.0 +/- 2.3 mmol/liter), while pH dropped from 7.43 +/- 0.03 to 7.11 +/- 0.02. Oxygen consumption remained below baseline. In four flaps thrombosis occurred within 6 hours; no flap survived 48 hours. The results of this study do not encourage clinical application of the concept of flow reversal. 相似文献