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991.
Bonazzi M Spanò S Turacchio G Cericola C Valente C Colanzi A Kweon HS Hsu VW Polishchuck EV Polishchuck RS Sallese M Pulvirenti T Corda D Luini A 《Nature cell biology》2005,7(6):570-580
Membrane fission is a fundamental step in membrane transport. So far, the only fission protein machinery that has been implicated in in vivo transport involves dynamin, and functions in several, but not all, transport pathways. Thus, other fission machineries may exist. Here, we report that carboxy-terminal binding protein 3/brefeldin A-ribosylated substrate (CtBP3/BARS) controls fission in basolateral transport from the Golgi to the plasma membrane and in fluid-phase endocytosis, whereas dynamin is not involved in these steps. Conversely, CtBP3/BARS protein is inactive in apical transport to the plasma membrane and in receptor-mediated endocytosis, both steps being controlled by dynamin. This indicates that CtBP3/BARS controls membrane fission in endocytic and exocytic transport pathways, distinct from those that require dynamin. 相似文献
992.
Prohibitin is required for Ras-induced Raf-MEK-ERK activation and epithelial cell migration 总被引:6,自引:0,他引:6
Rajalingam K Wunder C Brinkmann V Churin Y Hekman M Sievers C Rapp UR Rudel T 《Nature cell biology》2005,7(8):837-843
Ras proteins control the signalling pathways that are responsible for normal growth and malignant transformation. Raf protein kinases are direct Ras effector proteins that initiate the mitogen-activated protein kinase (MAPK) cascade, which mediates diverse biological functions such as cell growth, survival and differentiation. Here we show that prohibitin, a ubiquitously expressed and evolutionarily conserved protein is indispensable for the activation of the Raf-MEK-ERK pathway by Ras. The membrane targeting and activation of C-Raf by Ras needs prohibitin in vivo. In addition, direct interaction with prohibitin is required for C-Raf activation. C-Raf kinase fails to interact with the active Ras induced by epidermal growth factor in the absence of prohibitin. Moreover, in prohibitin-deficient cells the adhesion complex proteins cadherin and beta-catenin relocalize to the plasma membrane and thereby stabilize adherens junctions. Our data show an unexpected role of prohibitin in the activation of the Ras-Raf signalling pathway and in modulating epithelial cell adhesion and migration. 相似文献
993.
994.
Qiong?Wang Inga?M?Melzer Martin?Kruse Claudia?Sander-Juelch Martin?WieseEmail author 《Kinetoplastid biology and disease》2005,4(1):6
Background
Leishmania parasites undergo profound morphological and biochemical changes while passing through their life cycle. Protein kinases have been shown to be involved in the differentiation from the extracellular flagellated promastigotes to the intracellular "non-flagellated" amastigotes and vice versa. Moreover, these enzymes are likely involved in the regulation of the proliferation of the different life stages. 相似文献995.
Ines Gockel Sina Heckhoff Claudia M Messow Werner Kneist Theodor Junginger 《World journal of surgical oncology》2005,3(1):1-11
Background
Goblet cell carcinoid (GCC) of the appendix is a rare neoplasm that share histological features of both adenocarcinoma and carcinoid tumor. While its malignant potential remains unclear, GCC's are more aggressive than conventional carcinoid. The clinical presentations of this neoplasm are also varied. This review summarizes the published literature on GCC of the appendix. The focus is on its diagnosis, histopathological aspects, clinical manifestations, and management.Methods
Published studies in the English language between 1966 to 2004 were identified through Medline keyword search utilizing terms "goblet cell carcinoid," "adenocarcinoid", "mucinous carcinoid" and "crypt cell carcinoma" of the appendix.Results
Based on the review of 57 published papers encompassing nearly 600 diagnosed patients, the mean age of presentation for GCC of the appendix was 58.89 years with equal representation in both males and females. Accurate diagnosis of this neoplasm requires astute observations within an acutely inflamed appendix as this neoplasm has a prominent pattern of submucosal growth and usually lacks the formation of a well-defined tumor mass. The mesoappendix was involved in 21.64% followed by perineural involvement in 2.06%. The most common clinical presentations in order of frequency were acute appendicitis in 22.5%; asymptomatic in 5.4%; non-localized abdominal pain in 5.15% and an appendicular mass in 3.09%. The most common surgical treatment of choice was appendectomy with right hemicolectomy in 34.70% followed by simple appendectomy in 24.57%. Concomitant distant metastasis at diagnosis was present in 11.16% of patients with the ovaries being the most common site in 3.60% followed by disseminated abdominal carcinomatosis in 1.03%. Local lymph node involvement was seen in 8.76% of patients at the time of diagnosis. The reported 5-year survival ranges from 60 % to 84%. GCC's of the appendix remains a neoplasm of unpredictable biological behavior and thus warrants lifelong surveillance for recurrence of the disease upon diagnosis and successful surgical extirpation.Conclusion
GCC of the appendix is a rare neoplasm. Due to its wide range of presentation, this tumor should be considered as a possible diagnosis in many varied situations leading to abdominal surgery. Histopathological features such as increased number of Paneth cells, increased amount of mucin secretion and presence of pancreatic polypeptide may predict a more aggressive behavior. The advocated plan of management recommended for patients with tumors that involve the adjacent caecum or with high-grade tumors with histological features such as an increased mitotic rate involve initial appendectomy with completion right hemicolectomy due to the high possibility of local recurrence with intraperitoneal seeding prior to lymph node involvement and a 20% risk of metastatic behavior. In female patients with GCC of the appendix regardless of age, bilateral salpingo-oophorectomy is advocated. In cases with obvious spread of the disease chemotherapy, mostly with 5-FU and leucovorin is advised. Cytoreductive surgery with adjuvant intraperitoneal chemotherapy can offer improved survival in cases with advanced peritoneal dissemination. 相似文献996.
WW or WoW: the WW domains in a union of bliss 总被引:1,自引:0,他引:1
WW domains are small protein modules that recognize proline-rich peptide motifs or phosphorylated-serine/threonine proline sites in cognate proteins. Within host proteins these modules are joined to other protein domains or to a variety of catalytic domains acting together as adaptors or targeting anchors of enzymes. An important aspect of signaling by WW domains is their ability to recognize their cognate ligands in tandem. Tandem WW domains not only act in a synergistic manner but also appear to chaperone the function of each other. In this review, we focus on structure, function, and mechanism of the tandem WW domains co-operativity as well as independent actions. We emphasize here the implications of tandem arrangement and cooperative function of the domains for signaling pathways. 相似文献
997.
The "A Disintegrin And Metalloproteinase" (ADAM) protein family and the "A Disintegrin-like And Metalloproteinase with ThromboSpondin motifs" (ADAMTS) protein family are two related families of human proteins. The similarities and differences between these two families have been investigated using phylogenetic trees and homology modeling. The phylogenetic analysis indicates that the two families are well differentiated, even when only the common metalloprotease domain is taken into account. Within the ADAM family, several proteins are lacking the binding motif for the catalytic zinc in the active site and thus presumably lack any catalytic activity. These proteins tend to cluster within the ADAM phylogenetic tree and are expressed in specific tissues, suggesting a functional differentiation. The present analysis allows us to propose the following: (i) ADAMTS proteins have a conserved role in the human organism as proteases, with some differentiation in terms of substrate specificity; (ii) ADAM proteins can act as proteases and/or mediators of intermolecular interactions; (iii) proteolytically active ADAMs tend to be more ubiquitously expressed than the inactive ones. 相似文献
998.
Most principles of protein folding emerged from refolding studies in vitro on small, soluble proteins, because large ones tend to misfold and aggregate. We developed a folding assay allowing the study of large proteins in detergent such that the extent of cellular assistance required for proper folding can be determined. We identified a critical step in the in vivo folding pathway of influenza virus hemagglutinin (HA). Only the formation of the first few disulfides in the top domain of HA required the intact endoplasmic reticulum. After that, HA proceeded to fold efficiently in a very dilute solution, despite its size and complexity. This study paves the way for detailed structural analyses during the folding of complex proteins. 相似文献
999.
Gailus-Durner V Fuchs H Becker L Bolle I Brielmeier M Calzada-Wack J Elvert R Ehrhardt N Dalke C Franz TJ Grundner-Culemann E Hammelbacher S Hölter SM Hölzlwimmer G Horsch M Javaheri A Kalaydjiev SV Klempt M Kling E Kunder S Lengger C Lisse T Mijalski T Naton B Pedersen V Prehn C Przemeck G Racz I Reinhard C Reitmeir P Schneider I Schrewe A Steinkamp R Zybill C Adamski J Beckers J Behrendt H Favor J Graw J Heldmaier G Höfler H Ivandic B Katus H Kirchhof P Klingenspor M Klopstock T Lengeling A 《Nature methods》2005,2(6):403-404
1000.
2- and 8-alkynyl-9-ethyladenines: Synthesis and biological activity at human and rat adenosine receptors 总被引:1,自引:1,他引:0
Volpini R Costanzi S Lambertucci C Vittori S Martini C Trincavelli ML Klotz KN Cristalli G 《Purinergic signalling》2005,1(2):173-181
The synthesis of a series of 9-ethyladenine derivatives bearing alkynyl chains in 2- or 8-position was undertaken, based on the observation that replacement of the sugar moiety in adenosine derivatives with alkyl groups led to adenosine receptor antagonists. All the synthesized compounds were tested for their affinity at human and rat A1, A2A, and A3 adenosine receptors in binding assays; the activity at the human A2B receptor was determined in adenylyl cyclase experiments. Biological data showed that the 2-alkynyl derivatives possess good affinity and are slightly selective for the human A2A receptor. The same compounds tested on the rat A1 and A2A subtypes showed in general lower affinity for both receptors. On the other hand, the affinity of the 8-alkynyl derivatives at the human A1, A2A, and A2B receptors proved to be lower than that of the corresponding 2-alkynyl derivatives. On the contrary, the affinity of the same compounds for the human A3 receptor was improved, resulting in A3 selectivity. As in the case of the 2-alkynyl-substituted compounds, the 8-alkynyl derivatives showed decreased affinity for rat receptors. However, it is worthwhile to note that the 8-phenylethynyl-9-ethyladenine was the most active compound of the two series (Ki in the nanomolar range) at both the human and rat A3 subtype. Docking experiments of the 2- and 8-phenylethynyl-9-ethyladenines, at a rhodopsin-based homology model, gave a rational explanation of the preference of the human A3 receptor for the 8-substituted compound. 相似文献