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61.
Christopher M. Witham Aleshanee L. Paxman Lamprini Baklous Robert F. L. Steuart Benjamin L. Schulz Carl J. Mousley 《PLoS genetics》2021,17(8)
Translocation of secretory and integral membrane proteins across or into the ER membrane occurs via the Sec61 complex, a heterotrimeric protein complex possessing two essential sub-units, Sec61p/Sec61α and Sss1p/Sec61γ and the non-essential Sbh1p/Sec61β subunit. In addition to forming a protein conducting channel, the Sec61 complex maintains the ER permeability barrier, preventing flow of molecules and ions. Loss of Sec61 integrity is detrimental and implicated in the progression of disease. The Sss1p/Sec61γ C-terminus is juxtaposed to the key gating module of Sec61p/Sec61α and is important for gating the translocon. Inspection of the cancer genome database identifies six mutations in highly conserved amino acids of Sec61γ/Sss1p. We identify that five out of the six mutations identified affect gating of the ER translocon, albeit with varying strength. Together, we find that mutations in Sec61γ that arise in malignant cells result in altered translocon gating dynamics, this offers the potential for the translocon to represent a target in co-therapy for cancer treatment. 相似文献
62.
Johannes Lerchner Anne Schulz Theresa Poeschel Antje Wolf Tom Hartmann Florian Mertens Elke Boschke 《Engineering in Life Science》2012,12(6):615-620
We present a new chip calorimeter for fast and quantitative measurement of metabolic heat rates of microorganisms attached to magnetic beads. In biomagnetic separation (BMS) experiments, Escherichia coli K12 immobilized on nonspecifically functionalized beads has a specific heat rate of around 1 pW per cell at 37°C. Therefore, at least 2 × 104 bacteria are required to exceed the calorimetric signal resolution of 20 nW. If the samples to be analyzed have the original volume of 4 mL, bacteria at less than 104 cells mL?1 should be detectable. In practice, we achieved the detection of approximately 2 × 104 cells mL?1. The method presented here might also find some applications in the investigation of biofilms and study of biomolecular interactions. 相似文献
63.
The retro-analogue of glutathione disulfide was bound to the GSSG binding site of crystalline glutathione reductase. The binding mode revealed why the analogue is a very poor substrate in enzyme catalysis. The observed binding mode difference between natural substrate and retro-analogue is explained. 相似文献
64.
Assay of L-3-hydroxyacyl-coenzyme A dehydrogenase with substrates of different chain lengths 总被引:1,自引:0,他引:1
A method for assaying L-3-hydroxyacyl-CoA dehydrogenase (EC 1.1.1.35) which permits rate measurements with L-3-hydroxyacyl-CoA substrates of various chain lengths at physiological pH is described. The method is based on a coupled assay system in which 3-ketoacyl-CoA compounds formed by the dehydrogenase are cleaved by 3-ketoacyl-CoA thiolase (EC 2.3.1.16) in the presence of CoASH. The advantages of this assay method are its irreversibility and elimination of product inhibition. The assay procedure was used to determine the kinetic parameters (Km, Vmax) of pig heart L-3-hydroxyacyl-CoA dehydrogenase with several substrates of various chain lengths. The data obtained show the enzyme to be most active with medium-chain substrates whereas Km values for medium-chain and long-chain substrates are almost equal but much lower than those previously reported. 相似文献
65.
Julie Earl Daniel Rico Enrique Carrillo-de-Santa-Pau Benjamín Rodríguez-Santiago Marinela Méndez-Pertuz Herbert Auer Gonzalo Gómez Herbert Barton Grossman David G Pisano Wolfgang A Schulz Luis A Pérez-Jurado Alfredo Carrato Dan Theodorescu Stephen Chanock Alfonso Valencia Francisco X Real 《BMC genomics》2015,16(1)
Background
Urothelial bladder cancer is a highly heterogeneous disease. Cancer cell lines are useful tools for its study. This is a comprehensive genomic characterization of 40 urothelial bladder carcinoma (UBC) cell lines including information on origin, mutation status of genes implicated in bladder cancer (FGFR3, PIK3CA, TP53, and RAS), copy number alterations assessed using high density SNP arrays, uniparental disomy (UPD) events, and gene expression.Results
Based on gene mutation patterns and genomic changes we identify lines representative of the FGFR3-driven tumor pathway and of the TP53/RB tumor suppressor-driven pathway. High-density array copy number analysis identified significant focal gains (1q32, 5p13.1-12, 7q11, and 7q33) and losses (i.e. 6p22.1) in regions altered in tumors but not previously described as affected in bladder cell lines. We also identify new evidence for frequent regions of UPD, often coinciding with regions reported to be lost in tumors. Previously undescribed chromosome X losses found in UBC lines also point to potential tumor suppressor genes. Cell lines representative of the FGFR3-driven pathway showed a lower number of UPD events.Conclusions
Overall, there is a predominance of more aggressive tumor subtypes among the cell lines. We provide a cell line classification that establishes their relatedness to the major molecularly-defined bladder tumor subtypes. The compiled information should serve as a useful reference to the bladder cancer research community and should help to select cell lines appropriate for the functional analysis of bladder cancer genes, for example those being identified through massive parallel sequencing.Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1450-3) contains supplementary material, which is available to authorized users. 相似文献66.
Biological and molecular variability of human immunodeficiency virus type 2 isolates from The Gambia. 总被引:5,自引:9,他引:5 下载免费PDF全文
T F Schulz D Whitby J G Hoad T Corrah H Whittle R A Weiss 《Journal of virology》1990,64(10):5177-5182
Seven new human immunodeficiency virus type 2 (HIV-2) isolates (CBL-20 to CBL-26) from The Gambia were characterized. Their cytopathogenicity and growth in vitro correlated with the severity of clinical disease. CBL-22 was highly sensitive to neutralization by HIV-2 sera and was cross-neutralized by some HIV-1 sera. These findings, the differing sizes of envelope glycoproteins of individual isolates, and the sequence analysis of amplified regions of the viral DNAs show that these HIV-2 isolates from one geographical region in West Africa exhibit biological and genome variability comparable to that observed for HIV-1. 相似文献
67.
Siegel G Sternfeld L Gonzalez A Schulz I Schmid A 《The Journal of biological chemistry》2001,276(20):16986-16991
In pancreatic acinar cells analysis of the propagation speed of secretagogue-evoked Ca2+ waves can be used to examine coupling of hormone receptors to intracellular signal cascades that cause activation of protein kinase C or production of arachidonic acid (AA). In the present study we have investigated the role of cytosolic phospholipase A2 (cPLA2) and AA in acetylcholine (ACh)- and bombesin-induced Ca2+ signaling. Inhibition of cPLA2 caused acceleration of ACh-induced Ca2+ waves, whereas bombesin-evoked Ca2+ waves were unaffected. When enzymatic metabolization of AA was prevented with the cyclooxygenase inhibitor indomethacin or the lipoxygenase inhibitor nordihydroguaiaretic acid, ACh-induced Ca2+ waves were slowed down. Agonist-induced activation of cPLA2 involves mitogen-activated protein kinase (MAPK) activation. An increase in phosphorylation of p38(MAPK) and p42/44(MAPK) within 10 s after stimulation could be demonstrated for ACh but was absent for bombesin. Rapid phosphorylation of p38(MAPK) and p42/44(MAPK) could also be observed in the presence of cholecystokinin (CCK), which also causes activation of cPLA2. ACh-and CCK-induced Ca2+ waves were slowed down when p38(MAPK) was inhibited with SB 203580, whereas inhibition of p42/44(MAPK) with PD 98059 caused acceleration of ACh- and CCK-induced Ca2+ waves. The spreading of bombesin-evoked Ca2+ waves was affected neither by PD 98059 nor by SB 203580. Our data indicate that in mouse pancreatic acinar cells both ACh and CCK receptors couple to the cPLA2 pathway. cPLA2 activation occurs within 1-2 s after hormone application and is promoted by p42/44(MAPK) and inhibited by p38(MAPK). Furthermore, the data demonstrate that secondary (Ca2+-induced) Ca2+ release, which supports Ca2+ wave spreading, is inhibited by AA itself and not by a metabolite of AA. 相似文献
68.
Feral Horse (Equus caballus) impacts in northern Kosciuszko National Park, New South Wales, Australia are directly occurring in habitat of the nationally threatened Broad‐toothed Rat (Mastacomys fuscus). This species is endemic primarily to the mountain regions of south‐eastern mainland Australia and Tasmania, with a disjunct population at Barrington Tops. The Broad‐toothed Rat's preferred habitat is being increasingly impacted by browsing and trampling associated with the expansion of feral horse populations. This study surveyed 180 sites supporting preferred habitat for this species to determine Broad‐toothed Rat presence and relative abundance in relation to the level of feral horse impacts within the reserve. There was a significant negative relationship between feral horse impacts and both Broad‐toothed Rat presence and abundance. No scats were identified at localities where feral horse impacts were severe, and at moderate horse impact sites, there was a proportion (34%) without scats found. Locations with low horse impacts had little impact on Broad‐toothed Rat occurrence. As feral horse populations increase, Broad‐toothed Rat populations may be further impacted. Such impacts will be due to the loss of vegetation cover from feral horse trampling and grazing, making animals more vulnerable to predation by predators or impacting on their ability to disperse to more suitable habitat. Habitat remnants and vegetation corridors along drainage lines require protection from feral horses to prevent localized extinctions of Broad‐toothed Rat. 相似文献
69.
Lipidomic and transcriptomic analyses of Chlamydomonas reinhardtii under heat stress unveil a direct route for the conversion of membrane lipids into storage lipids 下载免费PDF全文
70.
Emily Sonestedt Sophie Hellstrand Christina-Alexandra Schulz Peter Wallstr?m Isabel Drake Ulrika Ericson Bo Gullberg Bo Hedblad Marju Orho-Melander 《PloS one》2015,10(4)