全文获取类型
收费全文 | 4821篇 |
免费 | 473篇 |
国内免费 | 2篇 |
专业分类
5296篇 |
出版年
2021年 | 48篇 |
2019年 | 46篇 |
2018年 | 50篇 |
2017年 | 65篇 |
2016年 | 81篇 |
2015年 | 144篇 |
2014年 | 154篇 |
2013年 | 205篇 |
2012年 | 270篇 |
2011年 | 253篇 |
2010年 | 174篇 |
2009年 | 145篇 |
2008年 | 216篇 |
2007年 | 221篇 |
2006年 | 193篇 |
2005年 | 229篇 |
2004年 | 198篇 |
2003年 | 185篇 |
2002年 | 170篇 |
2001年 | 132篇 |
2000年 | 130篇 |
1999年 | 109篇 |
1998年 | 70篇 |
1997年 | 63篇 |
1996年 | 72篇 |
1995年 | 62篇 |
1994年 | 53篇 |
1993年 | 50篇 |
1992年 | 81篇 |
1991年 | 83篇 |
1990年 | 78篇 |
1989年 | 68篇 |
1988年 | 58篇 |
1987年 | 44篇 |
1986年 | 49篇 |
1985年 | 61篇 |
1984年 | 46篇 |
1983年 | 48篇 |
1982年 | 39篇 |
1981年 | 45篇 |
1980年 | 33篇 |
1979年 | 44篇 |
1978年 | 36篇 |
1977年 | 45篇 |
1976年 | 49篇 |
1975年 | 36篇 |
1974年 | 47篇 |
1973年 | 35篇 |
1972年 | 36篇 |
1970年 | 37篇 |
排序方式: 共有5296条查询结果,搜索用时 15 毫秒
101.
Jennifer L. Belsky Alyssa J. Ashley Premal A. Bhatt Karen V. Gilbert Heather R. Joyce Chunhua Pan Horacio Pappa Samir Z. Wahab 《AAPS PharmSciTech》2010,11(2):994-1004
The water-insoluble procedures in US Pharmacopeia (USP) General Chapter Residual Solvents <467>, which are based on European Pharmacopoeia procedures, were optimized and modified before their inclusion in the chapter to improve their scope, performance, and ruggedness.
The optimized procedures use a static headspace introduction system with a gas chromatograph equipped with a flame ionization
detector. This article describes some of the key changes made to the USP published procedures, including use of dimethyl sulfoxide
(DMSO) or dimethylformamide (DMF) as the solvent, addition of 5 mL of water and 1 mL of sample (dissolved in DMSO or DMF)
to the headspace vial, use of a 3:1 GC split ratio, and use of new matrix-matched system suitability solutions. These procedures
were verified with two different active pharmaceutical ingredients—hydroxyzine pamoate and prednisone. In the investigation,
the more polar material (hydroxyzine pamoate) showed greater recoveries for the optimized procedures when prepared in DMSO.
The less polar material (prednisone) typically had greater recoveries in DMF for the optimized procedures. During experimentation,
insights into sample preparation, additional types of headspace instrumentation, solvent purity, and other parameters were
also gained. 相似文献
102.
Rachel Gilbert 《Inorganica chimica acta》2010,363(7):1462-1468
Unlike other chlorometallate complexes that catalyze the photodecomposition of haloalkanes through photodissociation of a chlorine atom, both and catalyze chloroform decomposition through a process that appears to involve C-H bond breakage from an excited state association complex with chloroform. This would account for the greatly retarded rate of decomposition in CDCl3 and for the generation of CCl4 as a side product. In chloroform, and are in slow equilibrium with each other. The rate for the conversion of - in chloroform at 23 °C obeys the expression (0.03 M−1 s−1) [][Cl−]. The equilibrium constant, K = [][Cl−]2/[]2, was estimated to be 3 × 10−3 M in CHCl3. 相似文献
103.
Goessling W North TE Lord AM Ceol C Lee S Weidinger G Bourque C Strijbosch R Haramis AP Puder M Clevers H Moon RT Zon LI 《Developmental biology》2008,320(1):161-174
Developmental signaling pathways hold the keys to unlocking the promise of adult tissue regeneration, and to inhibiting carcinogenesis. Patients with mutations in the Adenomatous Polyposis Coli (APC) gene are at increased risk of developing hepatoblastoma, an embryonal form of liver cancer, suggesting that Wnt affects hepatic progenitor cells. To elucidate the role of APC loss and enhanced Wnt activity in liver development, we examined APC mutant and wnt inducible transgenic zebrafish. APC+/− embryos developed enlarged livers through biased induction of hepatic gene programs and increased proliferation. Conversely, APC−/− embryos formed no livers. Blastula transplantations determined that the effects of APC loss were cell autonomous. Induction of wnt modulators confirmed biphasic consequences of wnt activation: endodermal pattern formation and gene expression required suppression of wnt signaling in early somitogenesis; later, increased wnt activity altered endodermal fate by enhancing liver growth at the expense of pancreas formation; these effects persisted into the larval stage. In adult APC+/− zebrafish, increased wnt activity significantly accelerated liver regeneration after partial hepatectomy. Similarly, liver regeneration was significantly enhanced in APCMin/+ mice, indicating the conserved effect of Wnt pathway activation in liver regeneration across vertebrate species. These studies reveal an important and time-dependent role for wnt signaling during liver development and regeneration. 相似文献
104.
Trucco Carlotta Rolli Véronique Oliver F. Javier Flatter Eric Masson Murielle Dantzer Françoise Neidergang Claude Dutrillaux Bernard Ménissier-de murcia Josiane de Murcia Gilbert 《Molecular and cellular biochemistry》1999,193(1-2):53-60
A dual approach to the study of poly (ADP-ribose)polymerase (PARP) in terms of its structure and function has been developed in our laboratory. Random mutagenesis of the DNA binding domain and catalytic domain of the human PARP, has allowed us to identify residues that are crucial for its enzymatic activity.In parallel PARP knock-out mice were generated by inactivation of both alleles by gene targeting. We showed that: (i) they are exquisitely sensitive to -irradiation, (ii) they died rapidly from acute radiation toxicity to the small intestine, (iii) they displayed a high genomic instability to -irradiation and MNU injection and, (iv) bone marrow cells rapidly underwent apoptosis following MNU treatment, demonstrating that PARP is a survival factor playing an essential and positive role during DNA damage recovery and survival. 相似文献
105.
The action of hydrogen peroxide on paired pulse and long-term potentiation in the hippocampus 总被引:1,自引:0,他引:1
The action of a reactive oxygen intermediate, that is, hydrogen peroxide (H2O2) on modulation of synaptic transmission was examined in the hippocampal brain slice preparation. Microinjection of H2O2 into the apical dendritic region of the CA1 pyramidal cells produced no change in either the pattern or amplitude of paired pulse facilitation compared to saline injection (control). Long term potentiation (LTP), induced by high frequency stimulation of homosynaptic inputs, however, was blocked by microinjection of H2O2 into the dendritic tree. LTP was seen in only 2 out of 10 slices investigated when treated with H2O2 while LTP was seen in 4 out of 5 slices when saline injected. The results suggest that a reactive oxygen intermediate can selectively modify synaptic mechanisms in the hippocampus. 相似文献
106.
Lucy I. Crouch Aurore Labourel Paul H. Walton Gideon J. Davies Harry J. Gilbert 《The Journal of biological chemistry》2016,291(14):7439-7449
Lignocellulosic biomass is a sustainable industrial substrate. Copper-dependent lytic polysaccharide monooxygenases (LPMOs) contribute to the degradation of lignocellulose and increase the efficiency of biofuel production. LPMOs can contain non-catalytic carbohydrate binding modules (CBMs), but their role in the activity of these enzymes is poorly understood. Here we explored the importance of CBMs in LPMO function. The family 2a CBMs of two monooxygenases, CfLPMO10 and TbLPMO10 from Cellulomonas fimi and Thermobispora bispora, respectively, were deleted and/or replaced with CBMs from other proteins. The data showed that the CBMs could potentiate and, surprisingly, inhibit LPMO activity, and that these effects were both enzyme-specific and substrate-specific. Removing the natural CBM or introducing CtCBM3a, from the Clostridium thermocellum cellulosome scaffoldin CipA, almost abolished the catalytic activity of the LPMOs against the cellulosic substrates. The deleterious effect of CBM removal likely reflects the importance of prolonged presentation of the enzyme on the surface of the substrate for efficient catalytic activity, as only LPMOs appended to CBMs bound tightly to cellulose. The negative impact of CtCBM3a is in sharp contrast with the capacity of this binding module to potentiate the activity of a range of glycoside hydrolases including cellulases. The deletion of the endogenous CBM from CfLPMO10 or the introduction of a family 10 CBM from Cellvibrio japonicus LPMO10B into TbLPMO10 influenced the quantity of non-oxidized products generated, demonstrating that CBMs can modulate the mode of action of LPMOs. This study demonstrates that engineered LPMO-CBM hybrids can display enhanced industrially relevant oxygenations. 相似文献
107.
108.
109.
Phosphatidylinositol-4,5-bisphosphate [PI(4,5)P?] plays a fundamental role in clathrin-mediated endocytosis. However, precisely how PI(4,5)P? metabolism is spatially and temporally regulated during membrane internalization and the functional consequences of endocytosis-coupled PI(4,5)P? dephosphorylation remain to be explored. Using cell-free assays with liposomes of varying diameters, we show that the major synaptic phosphoinositide phosphatase, synaptojanin 1 (Synj1), acts with membrane curvature generators/sensors, such as the BAR protein endophilin, to preferentially remove PI(4,5)P? from curved membranes as opposed to relatively flat ones. Moreover, in vivo recruitment of Synj1's inositol 5-phosphatase domain to endophilin-induced membrane tubules results in fragmentation and condensation of these structures largely in a dynamin-dependent fashion. Our study raises the possibility that geometry-based mechanisms may contribute to spatially restricting PI(4,5)P? elimination during membrane internalization and suggests that the PI(4,5)P?-to-PI4P conversion achieved by Synj1 at sites of high curvature may cooperate with dynamin to achieve membrane fission. 相似文献
110.