全文获取类型
收费全文 | 2321篇 |
免费 | 184篇 |
出版年
2023年 | 10篇 |
2022年 | 20篇 |
2021年 | 53篇 |
2020年 | 26篇 |
2019年 | 29篇 |
2018年 | 39篇 |
2017年 | 31篇 |
2016年 | 65篇 |
2015年 | 112篇 |
2014年 | 106篇 |
2013年 | 135篇 |
2012年 | 157篇 |
2011年 | 195篇 |
2010年 | 106篇 |
2009年 | 81篇 |
2008年 | 141篇 |
2007年 | 135篇 |
2006年 | 121篇 |
2005年 | 147篇 |
2004年 | 151篇 |
2003年 | 117篇 |
2002年 | 100篇 |
2001年 | 25篇 |
2000年 | 19篇 |
1999年 | 30篇 |
1998年 | 28篇 |
1997年 | 14篇 |
1996年 | 13篇 |
1995年 | 18篇 |
1994年 | 16篇 |
1993年 | 14篇 |
1992年 | 25篇 |
1991年 | 14篇 |
1990年 | 18篇 |
1989年 | 16篇 |
1988年 | 9篇 |
1987年 | 16篇 |
1986年 | 13篇 |
1985年 | 6篇 |
1984年 | 13篇 |
1983年 | 10篇 |
1982年 | 10篇 |
1981年 | 11篇 |
1980年 | 9篇 |
1979年 | 7篇 |
1978年 | 8篇 |
1977年 | 6篇 |
1976年 | 8篇 |
1973年 | 6篇 |
1967年 | 9篇 |
排序方式: 共有2505条查询结果,搜索用时 15 毫秒
21.
The cumulative effect of wetlands on stream water quality and quantity. A landscape approach 总被引:7,自引:0,他引:7
A method was developed to evaluate the cumulative effect of wetland mosaics in the landscape on stream water quality and quantity in the nine-county region surrounding Minneapolis—St. Paul, Minnesota. A Geographic Information System (GIS) was used to record and measure 33 watershed variables derived from historical aerial photos. These watershed variables were then reduced to eight principal components which explained 86% of the variance. Relationships between stream water quality variables and the three wetland-related principal components were explored through stepwise multiple regression analysis. The proximity of wetlands to the sampling station was related to principal component two, which was associated with decreased annual concentrations of inorganic suspended solids, fecal coliform, nitrates, specific conductivity, flow-weighted NH4 flow-weighted total P, and a decreased proportion of phosphorus in dissolved form(p < 0.05). Wetland extent was related to decreased specific conductivity, chloride, and lead concentrations. The wetland-related principal components were also associated with the seasonal export of organic matter, organic nitrogen, and orthophosphate. Relationships between water quality and wetlands components were different for time-weighted averages as compared to flow-weighted averages. This suggests that wetlands were more effective in removing suspended solids, total phosphorus, and ammonia during high flow periods but were more effective in removing nitrates during low flow periods. 相似文献
22.
The Sec1 Family: A Novel Family of Proteins Involved in Synaptic Transmission and General Secretion 总被引:10,自引:1,他引:9
Abstract: The Sec1 family, a novel family of proteins involved in synaptic transmission and general secretion, is described. To date, 14 members of this family have been identified: four yeast proteins, Sec1, Sly1, Slp1/Vps33, and Vps45/Stt10; three nematode proteins, Unc-18 and the homologues of Sly1 and Slp1; the Drosophila Rop; and six mammalian proteins, the rat Munc-18/n-Sec1/rbSec1A and rbSec1B, the mouse Munc-18b/muSec1 and Munc-18c, and the bovine Munc-18 and mSec1. The mammalian proteins share 44–63% sequence identity with the nematode Unc-18 and Drosophila Rop proteins and 20–29% with the yeast proteins and their nematode homologues. The Sec1 proteins are mostly hydrophilic and lack a transmembrane domain. Nevertheless, Sec1 proteins are found as membrane-bound proteins. Some of them are also found as soluble, cytoplasmic proteins. Binding of the rat brain Sec1 to the presynaptic membrane may be due to strong interaction with syntaxin, an integral component of this membrane. The rat brain Sec1 is also bound to Cdk5, a neural cyclin-dependent kinase. The Sec1 proteins play a positive role in exocytosis. Loss of function mutations in SEC1 , SLY1 , or SLP1 result in blocking of protein transport between distinct yeast subcellular compartments. Inactivation of unc-18 and rop results in inhibition of neurotransmitter release and, in the case of rop , inhibition of general secretion as well. In addition, studies of Rop and n-Sec1 indicate that they also play a negative role in synaptic transmission, mediated by their interaction with syntaxin. A working model addressing the dual regulative role of the Sec1 proteins in secretion is presented. 相似文献
23.
Kenji Takeuchi Sayumi Shibamoto Makio Hayakawa Takamitsu Hori Keiji Miyazawa Naomi Kitamura Fumiaki Ito 《Experimental cell research》1996,223(2):420
Hepatocyte growth factor (HGF) stimulated cell migration of human gastric carcinoma cell lines MKN1, MKN7, and MKN28. Epidermal growth factor (EGF) also stimulated the cell migration of these three cell lines. In MKN7 cells, HGF-stimulated cell migration was rather reduced in the presence of EGF, whereas such an observation was not made with MKN1 and MKN28 cells. Therefore, we compared the effect of EGF on HGF-stimulated HGF receptor phosphorylation in these cell lines. HGF induced a rapid tyrosine phosphorylation of the HGF receptor in all these cell lines. In MKN7 cells, the increased phosphorylation was further enhanced by EGF, although EGF alone did not affect tyrosine phosphorylation of the HGF receptor. In MKN1 and MKN28 cells, EGF did not influence tyrosine phosphorylation of the HGF receptor, whether HGF was present or not. The data presented here suggest that EGF negatively modulates the cellular response to HGF by increasing tyrosine phosphorylation of the HGF receptor in certain types of epithelial cells, e.g., MKN7 cells. 相似文献
24.
25.
Kyosuke Mushiake Fumiaki Motoyoshi Naomi Kondo Hiroyuki Shimizu Tadao Orii 《Biotherapy》1993,7(2):101-107
Five patients with common variable immunodeficiency treated in our hospital between December 1979 and December 1990 were given six kinds of intravenous immunoglobulin preparations (pepsin treated, S-sulfonated, polyethylene glycol treated, pH4 treated, alkylated, and pH4.25 formulation preparation) for replacement therapy. Duration of the therapy ranged from 7.6 to 11 years. Incidences of fever and acute infections were variable among patients, but no significant differences were seen in the incidences among periods given each preparation. Three cases revealed abnormal pulmonary functions in tests. Adverse reactions were rarely seen in our study periods, and no severe reactions were observed. No significant differences were seen in incidences of adverse reactions. Postinfusion levels of serum complement slightly decreased from preinfusion levels. However, the decrease in complement was not related to any adverse reaction. No long-term complications such as transmission of hepatitis have been observed. Our data suggest that no obvious differences exist between the efficacy and safety of each IVIG preparation. Differences of efficacy of IVIG replacement therapy may be due to the variable pathophysiology of each patient.Abbreviations CVID
common variable immunodeficiency
- IVIG
intravenous immunoglobulin 相似文献
26.
The role of the molybdenum cofactor (Mo cofactor) in the translocationof dimethyl sulfoxide (DMSO) reductase to the periplasmic spacewas studied in vivo by isolating chlorate-resistant mutantsof Rhodobacter sphaeroides f. sp. denitrificans. More than 50%of the chlorate-resistant mutants isolated were defective inthe biosynthesis of the Mo cofactor and all of these mutantsaccumulated the precursor form of the enzyme. About 45% of themutants contained the same level of Mo cofactor as the parentstrain and exhibited normal levels of DMSO reductase and nitratereductase activities when chlorate was absent from the medium,but the activities of these enzymes were depressed when chloratewas present. Much of the accumulated precursor form of the enzymein a Mo cofactor-deficient mutant was bound to the cytoplasmicmembrane and was sensitive to treatment with proteinase K fromthe periplasmic side of the membrane, an indication that theprecursor was exposed on the periplasmic surface of the membrane.The precursor accumulated on the membrane of the parent strainwhen molybdate was removed from the medium or upon additionof tungstate and this precursor was also sensitive to the treatmentwith proteinase K from the periplasmic side. These results suggestthat the Mo cofactor is necessary for proteolytic processingof the precursor to the mature enzyme on the periplasmic sideof the membrane, whereas binding of the precursor to the membraneand translocation across it can occur in the absence of thecofactor. Almost all of the Mo cofactor available for directreconstitution in vitro of nitrate reductase activity from thenit-l mutant of Neurospora crassa was present in the cytoplasmicfractions. (Received December 11, 1991; Accepted March 25, 1992) 相似文献
27.
By monitoring 45Ca2+ influx and efflux from oocytes a transient increase followed by a transient decrease in the Ca2+-content of progesterone-treated oocytes was observed. Chelation of intracellular Ca2+ with EGTA or BAPTA-type buffers inhibited progesterone-induced GVBD. Buffers with a mid-range Kd (∼1.5 μm) were most effective in inhibiting GVBD whereas buffers with a Kd above or below this value were less effective. These observations indicate that intracellular Ca2+, probably in the form of a localized release, is required for progesterone-induced oocyte maturation. However, Ca2+ alone was insufficient to induce GVBD. When the effects of nocodazole and taxol upon this Ca2+-requirement were tested, we observed that taxol-induced microtubule polymerization not only delayed progesterone-induced
GVBD but also completely inhibited it in combination with BAPTA-AM. Conversely, nocodazole-induced microtubule depolymerization
in combination with ionophore A23187 not only accelerated progesterone-induced GVBD, but also induced GVBD in the absence
of progesterone. The combined treatment of oocytes with nocodazole and InsP3, or with cold treatment and ionophore A23187 also induced GVBD in the absence of progesterone. Thus, Ca2+ and microtubule depolymerization synergistically promote GVBD. In both nocodazole- and cold-treated oocytes, the GV was displaced
to the periphery of the oocyte and underwent GVBD when treated with A23187. However, when the GV was displaced to the cortex
by a centrifugal force under conditions that would not cause microtubule depolymerization and the oocyte was treated with
A23187, oocytes did not undergo GVBD.
Received: 19 January 1996 / Accepted: 21 May 1996 相似文献
28.
Tomomi Hidaka Masao Goda Tomohisa Kuzuyama Naomi Takei Makoto Hidaka Haruo Seto 《Molecular & general genetics : MGG》1995,249(3):274-280
The biosynthetic pathway for production of the antibiotic fosfomycin by Streptomyces wedmorensis consists of four steps including the formation of a C-P bond and an epoxide. Fosfomycin production genes were cloned from genomic DNA using S. wedmorensis mutants blocked at different steps of the biosynthetic pathway. Four genes corresponding to each of the biosynthetic steps were found to be clustered in a DNA fragment of about 5 kb. Nucleotide sequencing of a large fragment revealed the presence of ten open reading frames, including the four biosynthetic genes and six genes with unknown functions. 相似文献
29.
Shunji Tomatsu Seiji Fukuda Alan Cooper James E. Wraith Atsushi Uchiyama Toshinori Hori Yoshinori Nakashima Naoto Yamada Kazuko Sukegawa Naomi Kondo Yasuyuki Suzuki Nobuyuki Shimozawa Tadao Orii 《Human genetics》1995,95(4):376-381
Ninety-six alleles (36 alleles of Japanese and 60 of Caucasian origin) from forty-eight patients with mucopolysaccharidosis IVA were investigated for structural gene alterations using Southern blot analysis. All patients had a previously demonstrated deficiency of N-acetylgalactosamine-6-sulfate-sulfatase and exhibited a wide spectrum of clinical severity. Initially, using the fulllength cDNA as a probe, five of 36 chromosomes from the Japanese patients revealed similar rearrangements with respect to DNA digested with BamHI, SacI, and XhoI. Subsequent analysis using seven genomic fragments, covering the entire gene, enhanced the detection of aberrant fragments produced by the above restriction enzymes. Conversely, the 60 chromosomes of Caucasian origin revealed no evidence of large structural rearrangements when analyzed by these methods. There was a statistically significant difference between the two populations (P < 0.01). A severely affected Japanese patient showed structural rearrangements on both chromosomes by means of BamHI blots. An 8.0-kb fragment and a highly polymorphic 7.0-kb to 11.0-kb fragment present in normal individuals disappeared and two aberrant fragments of 11.5 kb and 12.0 kb were observed. Three other Japanese patients also showed these two aberrant fragments, in addition to the normal fragment pattern, and were thus heterozygous for this rearrangement. Interpretation of Southern blots was difficult because of the complexity of polymorphic bands resulting from variable number of tandem repeat elements. However, by utilizing these aberrant fragments or polymorphic bands, carrier detection was effective, even in families with poorly characterized mutations. Hybridization with probe MG-A (5end genomic probe in intron 1) showed a 8.4-kb fragment in BamHI blots of one Japanese and one Caucasian patient; XhoI, SacI, and EcoRI blots were normal. Since this BamHI alteration was also observed in one normal control, it appears to be a rare nonpathological polymorphism. 相似文献
30.
Hideki Iwata Shunji Tomatsu Seiji Fukuda Atsushi Uchiyama G. M. M. Rezvi Tatsuya Ogawa Toshinori Hori Yoshihiro Nakashima Atsushi Yamagishi Kazuko Sukegawa Nobuyuki Shimozawa Yasuyuki Suzuki Naomi Kondo Tadao Orii 《Human genetics》1995,95(3):257-264
Seven different restriction fragment length polymorphisms (RFLPs) at the N-acetylgalactosamine-6-sulfate sulfatase (GALNS) locus were analyzed using Southern blotting and polymerase chain reaction based techniques to search for the frequency of each RFLP produced by StyI, SphI, HaeIII, StuI, HapII, XhoI, and BamHI restriction endonucleases, respectively, in 36 mutant alleles, including two sibling cases and 100 normal alleles. Calculation of heterozygosity indexes showed that these RFLPs were polymorphic, ranging from 0.31 to 0.69 in mucopolysaccharidosis IVA (MPS IVA) patients compared with 0.21 to 0.65 in normal individuals. There was some significant difference in several RFLPs and in the combination with four kinds of RFLPs (SphI, StuI, HapII, XhoI polymorphisms). The normal alleles were composed of 13 different RFLPs haplotypes; the most common among the Japanese population carrying normal alleles was haplotype 8 (bDEF1) (31.3%), the others being dispersed. The same haplotype 8 was the most frequent in the mutant alleles (44.4%), with seven further haplotypes. These findings revealed the striking variety of polymorphic haplotypes in the MPS IVA gene. By using these five kinds of RFLPs, we examined the theoretical informativity of haplotype analysis in heterozygote detection in nine unrelated MPS IVA families and ten unrelated normal families. All the members of the MPS IVA families studied were diagnosed as a patient, carrier, or noncarrier. We propose that prenatal diagnosis or family analysis in cases in which mutations have not been characterized is now feasible. 相似文献