全文获取类型
收费全文 | 2100篇 |
免费 | 108篇 |
国内免费 | 2篇 |
专业分类
2210篇 |
出版年
2023年 | 25篇 |
2022年 | 54篇 |
2021年 | 85篇 |
2020年 | 51篇 |
2019年 | 50篇 |
2018年 | 66篇 |
2017年 | 63篇 |
2016年 | 74篇 |
2015年 | 102篇 |
2014年 | 129篇 |
2013年 | 144篇 |
2012年 | 179篇 |
2011年 | 160篇 |
2010年 | 96篇 |
2009年 | 75篇 |
2008年 | 98篇 |
2007年 | 98篇 |
2006年 | 88篇 |
2005年 | 66篇 |
2004年 | 75篇 |
2003年 | 56篇 |
2002年 | 40篇 |
2001年 | 26篇 |
2000年 | 39篇 |
1999年 | 28篇 |
1998年 | 20篇 |
1997年 | 12篇 |
1996年 | 12篇 |
1995年 | 4篇 |
1994年 | 5篇 |
1993年 | 7篇 |
1992年 | 23篇 |
1991年 | 18篇 |
1990年 | 15篇 |
1989年 | 15篇 |
1988年 | 16篇 |
1987年 | 4篇 |
1986年 | 17篇 |
1985年 | 12篇 |
1984年 | 6篇 |
1983年 | 6篇 |
1982年 | 5篇 |
1981年 | 3篇 |
1980年 | 5篇 |
1979年 | 5篇 |
1978年 | 5篇 |
1977年 | 3篇 |
1972年 | 4篇 |
1970年 | 3篇 |
1969年 | 3篇 |
排序方式: 共有2210条查询结果,搜索用时 0 毫秒
101.
Wang W Dong C McNeil M Kaur D Mahapatra S Crick DC Naismith JH 《Journal of molecular biology》2008,381(1):129-140
In Mycobacterium tuberculosis, two related Z-prenyl diphosphate synthases, E,Z-farnesyl diphosphate synthase (Rv1086) and decaprenyl diphosphate synthase (Rv2361c), work in series to synthesize decaprenyl phosphate (C50) from isopentenyl diphosphate and E-geranyl diphosphate. Decaprenyl phosphate plays a central role in the biosynthesis of essential mycobacterial cell wall components, such as the mycolyl-arabinogalactan-peptidoglycan complex and lipoarabinomannan; thus, its synthesis has attracted considerable interest as a potential therapeutic target. Rv1086 is a unique prenyl diphosphate synthase in that it adds only one isoprene unit to geranyl diphosphate, generating the 15-carbon product (E,Z-farnesyl diphosphate). Rv2361c then adds a further seven isoprene units to E,Z-farnesyl diphosphate in a processive manner to generate the 50-carbon prenyl diphosphate, which is then dephosphorylated to generate a carrier for activated sugars. The molecular basis for chain-length discrimination by Rv1086 during synthesis is unknown. We also report the structure of apo Rv1086 with citronellyl diphosphate bound and with the product mimic E,E-farnesyl diphosphate bound. We report the structures of Rv2361c in the apo form, with isopentenyl diphosphate bound and with a substrate analogue, citronellyl diphosphate. The structures confirm the enzymes are very closely related. Detailed comparison reveals structural differences that account for chain-length control in Rv1086. We have tested this hypothesis and have identified a double mutant of Rv1086 that makes a range of longer lipid chains. 相似文献
102.
Proline is emerging as a critical component of drought tolerance and fine tuning of its metabolism under stress affects the plants sensitivity and response to stress. Thus the study was carried out to analyse the effect of water deficit on the proline content and principal enzymes involved in its synthesis (Δ1-pyrolline-carboxylate synthetase) and catabolism (proline dehydrogenase) at different developmental stages and in different organs (roots, nodules, leaves, pod wall, and seeds) of two chickpea (Cicer arietinum L.) cultivars differing in drought tolerance (drought tolerant ICC4958 and drought sensitive ILC3279). It was observed that increased Δ1-pyrolline-carboxylate synthetase activity under moderate stress in roots and nodules of ICC4958 caused an increase in proline content during initiation of reproductive development whereas increased proline dehydrogenase activity in nodules and leaves at this period helped to maintain reducing power and energy supply in tissues and proper seed development as seed biomass increased consistently up to maturity. On the other hand, roots and nodules of ILC3279 responded to stress by increasing proline content after the developmental phase of reproductive organs was over (near maturity) which negatively affected the response of pod wall to stress. Concurrent increase in activities of Δ1-pyrolline-carboxylate synthetase and proline dehydrogenase in pod wall of ILC3279 aggravated the oxidative stress and affected seed development as seed biomass initially increased rapidly under stress but was unaffected near maturity. 相似文献
103.
104.
Chloe Louise Rackham Paramjeet Kaur Dhadda Pedro Cesar Chagastelles Sian Jazmine Shakara Simpson Anshi Anjili Dattani James Edward Bowe Peter Martin Jones Aileen Jean Fiona King 《Cytotherapy》2013,15(4):449-459
Background aimsWe recently showed that co-transplantation of mesenchymal stromal cells (MSCs) improves islet function and revascularization in vivo. Pre-transplant islet culture is associated with the loss of islet cells. MSCs may enhance islet cell survival or function by direct cell contact mechanisms and soluble mediators. We investigated the capacity of MSCs to improve islet cell survival or β-cell function in vitro using direct and indirect contact islet-MSC configurations. We also investigated whether pre-culturing islets with MSCs improves islet transplantation outcome.MethodsThe effect of pre-culturing islets with MSCs on islet function in vitro was investigated by measuring glucose-stimulated insulin secretion. The endothelial cell density of fresh islets and islets cultured with or without MSCs was determined by immunohistochemistry. The efficacy of transplanted islets was tested in vivo using a syngeneic streptozotocin-diabetic minimal islet mass model. Graft function was investigated by monitoring blood glucose concentrations.ResultsIndirect islet-MSC co-culture configurations did not improve islet function in vitro. Pre-culturing islets using a direct contact MSC monolayer configuration improved glucose-stimulated insulin secretion in vitro, which correlated with superior islet graft function in vivo. MSC pre-culture had no effect on islet endothelial cell number in vitro or in vivo.ConclusionsPre-culturing islets with MSCs using a direct contact configuration maintains functional β-cell mass in vitro and the capacity of cultured islets to reverse hyperglycemia in diabetic mice. 相似文献
105.
N Norais J A Hall L Gross D Tang S Kaur S H Chamberlain R L Burke F Marcus 《Journal of virology》1996,70(8):5716-5719
As part of our vaccine program, we have purified a recombinant form of human cytomegalovirus glycoprotein B that is able to induce high titers of virus-neutralizing antibodies. The isolated protein was found to be phosphorylated at a serine residue in position -7 from the C terminus of the protein. The corresponding synthetic peptide, HLKDSDEEENV, was an efficient in vitro substrate of casein kinase II. 相似文献
106.
Increased oxidative stress and reduction in antioxidant enzymes have been suggested to be involved in the pathophysiology of congestive heart failure subsequent to myocardial infarction (MI). The objective of the present study was to characterize changes in the mRNA abundance and protein levels for the enzymatic antioxidants, superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase during the sequelae of congestive heart failure in rats. MI was produced by the ligation of the left coronary artery and hearts from controls and 1, 4 and 16 week PMI groups were analyzed. Losartan treatment (2 mg/ml in drinking water, daily) was started at 4 weeks and continued for 12 weeks. The mRNA levels for SOD were reduced by about 40% at 1-week PMI, were near to the control levels at 4-week PMI and at 16 weeks PMI, the levels were reduced by about 73% below the controls. GSHPx mRNA levels remained unchanged at all time points. The mRNA levels for catalase remained unchanged at 1 and 4 weeks PMI and were significantly reduced by about 44% at 16 weeks PMI as compared to the controls. The protein levels for MnSOD, CuZnSOD, GSHPx at 1 and 16 weeks remained unchanged in treated and untreated PMI groups. However, the protein levels for catalase was significantly increased in the control and PMI groups treated with Losartan. It is concluded that changes in the SOD and catalase activities during severe heart failure correlated with changes in mRNA for these enzymes. The precise mechanism/s for the improvement in antioxidant reserve and protein levels after Losartan treatment is/are unclear at this time. 相似文献
107.
A plasmid-encoded anion-translocating ATPase 总被引:1,自引:0,他引:1
B P Rosen C M Hsu C E Karkaria P Kaur J B Owolabi L S Tisa 《Biochimica et biophysica acta》1990,1018(2-3):203-205
An anion-translocating ATPase has been identified as the product of the arsenical resistance operon of resistance plasmid R773. When expressed in Escherichia coli this ATP-driven oxyanion pump catalyzes extrusion of the oxyanions arsenite, antimonite and arsenate. Maintenance of a low intracellular concentration of oxyanion produces resistance to the toxic agents. The pump is composed of two polypeptides, the products of the arsA and arsB genes. This two-subunit enzyme produces resistance to arsenite and antimonite. A third gene, arsC, expands the substrate specificity to allow for arsenate pumping and resistance. 相似文献
108.
Kaur A Singh R Dey CS Sharma SS Bhutani KK Singh IP 《Indian journal of experimental biology》2010,48(3):314-317
Hexane, chloroform and ethyl acetate extracts (100 microg/ml) of Alpinia galanga rhizomes exhibited significant activity in vitro against promastigotes of L. donovani. Twelve compounds namely, methyleugenol (1), p-coumaryl diacetate (2), 1'-acetoxychavicol acetate (3), 1'-acetoxyeugenol acetate (4), trans-p-acetoxycinnamyl alcohol (5), trans-3,4-dimethoxycinnamyl alcohol (6), p-hydroxybenzaldehyde (7), p-hydroxycinnamaldehyde (8), trans-p-coumaryl alcohol (9), galangin (10), trans-p-coumaric acid (11) and galanganol B (12) were isolated from these extracts. Of these, compounds 2, 3, 4 and 5 were found most active in vitro against promastigotes of L. donovani with IC50 values of 39.3, 32.9, 18.9 and 79.9 microM respectively. This is the first report of antileishmanial activity of the extracts and isolated constituents of A. galanga. 相似文献
109.
Yangjin Kim Hyun Geun Lee Nina Dmitrieva Junseok Kim Balveen Kaur Avner Friedman 《PloS one》2014,9(7)
Oncolytic viruses are genetically engineered viruses that are designed to kill cancer cells while doing minimal damage to normal healthy tissue. After being injected into a tumor, they infect cancer cells, multiply inside them, and when a cancer cell is killed they move on to spread and infect other cancer cells. Chondroitinase ABC (Chase-ABC) is a bacterial enzyme that can remove a major glioma ECM component, chondroitin sulfate glycosoamino glycans from proteoglycans without any deleterious effects in vivo. It has been shown that Chase-ABC treatment is able to promote the spread of the viruses, increasing the efficacy of the viral treatment. In this paper we develop a mathematical model to investigate the effect of the Chase-ABC on the treatment of glioma by oncolytic viruses (OV). We show that the model''s predictions agree with experimental results for a spherical glioma. We then use the model to test various treatment options in the heterogeneous microenvironment of the brain. The model predicts that separate injections of OV, one into the center of the tumor and another outside the tumor will result in better outcome than if the total injection is outside the tumor. In particular, the injection of the ECM-degrading enzyme (Chase-ABC) on the periphery of the main tumor core need to be administered in an optimal strategy in order to infect and eradicate the infiltrating glioma cells outside the tumor core in addition to proliferative cells in the bulk of tumor core. The model also predicts that the size of tumor satellites and distance between the primary tumor and multifocal/satellite lesions may be an important factor for the efficacy of the viral therapy with Chase treatment. 相似文献
110.
Satyendra Chandra Tripathi Ajay Matta Jatinder Kaur Jorg Grigull Shyam Singh Chauhan Alok Thakar Nootan Kumar Shukla Ritu Duggal Siddhartha DattaGupta Ranju Ralhan K. W. Michael Siu 《PloS one》2010,5(8)