全文获取类型
收费全文 | 1142篇 |
免费 | 75篇 |
出版年
2024年 | 4篇 |
2023年 | 15篇 |
2022年 | 24篇 |
2021年 | 43篇 |
2020年 | 28篇 |
2019年 | 39篇 |
2018年 | 41篇 |
2017年 | 26篇 |
2016年 | 39篇 |
2015年 | 47篇 |
2014年 | 75篇 |
2013年 | 69篇 |
2012年 | 73篇 |
2011年 | 88篇 |
2010年 | 49篇 |
2009年 | 34篇 |
2008年 | 60篇 |
2007年 | 53篇 |
2006年 | 45篇 |
2005年 | 43篇 |
2004年 | 46篇 |
2003年 | 41篇 |
2002年 | 40篇 |
2001年 | 24篇 |
2000年 | 12篇 |
1999年 | 16篇 |
1998年 | 8篇 |
1997年 | 8篇 |
1996年 | 7篇 |
1995年 | 3篇 |
1994年 | 4篇 |
1992年 | 17篇 |
1991年 | 11篇 |
1990年 | 8篇 |
1989年 | 7篇 |
1988年 | 3篇 |
1987年 | 8篇 |
1986年 | 8篇 |
1985年 | 3篇 |
1984年 | 8篇 |
1983年 | 8篇 |
1981年 | 4篇 |
1980年 | 3篇 |
1979年 | 4篇 |
1978年 | 3篇 |
1976年 | 2篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1972年 | 2篇 |
1971年 | 2篇 |
排序方式: 共有1217条查询结果,搜索用时 15 毫秒
291.
Approaches to increasing the salt tolerance of wheat and other cereals 总被引:28,自引:0,他引:28
This review describes physiological mechanisms and selectable indicators of gene action, with the aim of promoting new screening methods to identify genetic variation for increasing the salt tolerance of cereal crops. Physiological mechanisms that underlie traits for salt tolerance could be used to identify new genetic sources of salt tolerance. Important mechanisms of tolerance involve Na+ exclusion from the transpiration stream, sequestration of Na+ and Cl- in the vacuoles of root and leaf cells, and other processes that promote fast growth despite the osmotic stress of the salt outside the roots. Screening methods for these traits are discussed in relation to their use in breeding, particularly with respect to wheat. Precise phenotyping is the key to finding and introducing new genes for salt tolerance into crop plants. 相似文献
292.
Artificial proteins potentially barrier-free in the folding kinetics are approached computationally under the guidance of protein-folding theories. The smallest and fastest folding globular protein triple-helix-bundle (THB) is so modified as to minimize or eliminate its presumed barriers in folding speed. As the barriers may reside in the ordering of either secondary or tertiary structure, the elements of both secondary and tertiary structure in the protein are targeted for prenucleation with suitable stereochemically constrained amino acid residues. The required elements of topology and sequence for the THB are optimized independently; first the topology is optimized with simulated annealing in polypeptides of highly simplified alphabet; next, the sequence in side chains is optimized using the standard inverse design methods. The resultant three best-adapted THBs, variable in topology and distinctive in sequences, are assessed by comparing them with a few benchmark proteins. The results of mainly molecular dynamics (MD) comparisons, undertaken in explicit water at different temperatures, show that the designed sequences are favorably placed against the chosen benchmarks as THB proteins potentially thermostable in the native folds. Folding simulation experiments with MD establish that the designed sequences are rapid in the folding of individual helices, but not in the evolution of tertiary structure; energetic cum topological frustrations remain but could be the artifacts of the starting conformations that were chosen in the THBs in the folding simulations. Overall, a practical high-throughput approach for de novo protein design has been developed that may have fruitful application for any type of tertiary structure. 相似文献
293.
Vanadium is a metal widely distributed in the environment. It is also a dietary micronutrient. It has shown insulin mimetic and chemopreventive properties and has been considered as an important pharmacological agent. In this study, we evaluated the apoptogenic role of vanadium on human breast cancer cell line MCF7. Exposure of MCF7 cells to vanadium led to the induction of apoptosis in a dose-dependent manner. Percentage of apoptosis was maximum (42.5%) at the highest non-toxic dose (250 microM). It was found that vanadium treatment brought about a prominent chromatin condensation, cell cycle arrest leading to apoptosis. These apoptosis based assays demonstrate that vanadium has the potential to be developed into an anti-cancer drug in the near future. 相似文献
294.
295.
Tahseldar-Roumieh R Ghali-Ghoul R Lugnier C Sabra R 《American journal of physiology. Heart and circulatory physiology》2006,290(1):H481-H488
Previous studies suggested that increased activity of phosphodiesterase (PDE)5 in the kidneys of cirrhotic rats contributes to sodium retention. This study examined the role of PDE5 in the changes in vascular reactivity, hemodynamics, and sodium excretion in rats with liver cirrhosis. Four weeks after bile duct ligation (BDL) or sham operation (SO), in vitro reactivity of aortic rings to various agents and in vivo effects of a PDE5-selective inhibitor [1,3-dimethyl-6-(2-propoxy-5-methanesulfonylamidophenyl)pyrazolo[3,4d]-pyrimidin-4-(5H)-one, DMPPO] were studied. The vasodilator responses to nitroglycerin and S-nitroso-N-acetyl-penicillamine (SNAP) in phenylephrine-precontracted rings without endothelium were attenuated in BDL compared with SO rats. Pretreatment with DMPPO (0.1 microM) enhanced these responses and eliminated the differences between the two groups. Vasodilation to DMPPO itself was also less in BDL rats. The responses to phenylephrine were attenuated in endothelium-rich aorta from BDL relative to SO rats, but they were similar in endothelium-denuded aorta and remained similar despite preincubation with SNAP (0.1 microM) alone or with SNAP and DMPPO. In vivo, BDL rats were vasodilated relative to SO rats; DMPPO (5 mg/kg i.v.) decreased arterial pressure and vascular resistance in both groups equally and caused significant increase in sodium excretion in BDL rats only. In conclusion, the results are in accordance with a possible increase in PDE5 activity in aorta and kidney of cirrhotic rats that results in reduced responses to NO donors and contributes to the increase in sodium retention. PDE5 inhibitors may ameliorate sodium retention in cirrhosis but may worsen vasodilation. Examining the effect of PDE5 inhibitors after chronic administration will be more revealing. 相似文献
296.
Introduction: Quality assurance guidelines for the UK cervical screening programme recommend that more than 80% of cervical samples from women aged 20–50 years should contain adequate numbers of Transformation zone (TZ) cells i.e. 10 or more endocervical or squamous metaplastic cells. This study was conducted to assess the frequency of TZ component in Liquid Based Cytology (LBC) both for ThinPrep (TP) and SurePath (SP) LBC. Also to assess the degree to which this is recorded by individual screeners and to determine the percentage of samples with evidence of TZ component for the different smear takers.
Method: All LBC cervical specimens received at a tertiary cytology centre in the year 2004 from women aged 20–50 years were included in the study. Evidence of TZ sampling was recorded as: TP = TZ present (10 or more TZ cells)TA = TZ absentTS = TZ scanty (less than 10 TZ cells)TN = atrophic smears, TZ cells not recognisable
Results: The total number of LBC cervical cases was 7445. TP = 4300 (mostly primary care) and SP = 3145 (mostly colposcopy). Overall TZ sampling rate in LBC was 82%. TP = 77.17%; SP = 88.24%. When scanty TZ was included, the standard was met for both systems (TP = 93.7%; SP = 88.24%). Presence/absence of TZ component was recorded in 6370 cases (85.1%); range 0%–97.79%. 56.7% of smear takers achieved the minimum standard for TZ sampling.
Discussion: The percentage of ThinPrep samples containing adequate TZ cells was 77.17% compared to SurePath, which was 88.24%. This may be due to different patient populations i.e. primary care versus colposcopy. Screeners recorded TZ sampling in approximately 85% of samples. 56.7% of smear takers met the standard for TZ sampling. 相似文献
Method: All LBC cervical specimens received at a tertiary cytology centre in the year 2004 from women aged 20–50 years were included in the study. Evidence of TZ sampling was recorded as: TP = TZ present (10 or more TZ cells)TA = TZ absentTS = TZ scanty (less than 10 TZ cells)TN = atrophic smears, TZ cells not recognisable
Results: The total number of LBC cervical cases was 7445. TP = 4300 (mostly primary care) and SP = 3145 (mostly colposcopy). Overall TZ sampling rate in LBC was 82%. TP = 77.17%; SP = 88.24%. When scanty TZ was included, the standard was met for both systems (TP = 93.7%; SP = 88.24%). Presence/absence of TZ component was recorded in 6370 cases (85.1%); range 0%–97.79%. 56.7% of smear takers achieved the minimum standard for TZ sampling.
Discussion: The percentage of ThinPrep samples containing adequate TZ cells was 77.17% compared to SurePath, which was 88.24%. This may be due to different patient populations i.e. primary care versus colposcopy. Screeners recorded TZ sampling in approximately 85% of samples. 56.7% of smear takers met the standard for TZ sampling. 相似文献
297.
M. Holbrook J. Roebuck D. N. Rana J. Marshall S. Roberts & M. Desai 《Cytopathology》2006,17(S1):16-16
Although the characteristics of false negative conventional smears have been well documented there is limited literature available for Liquid Based Cytology (LBC), especially with regard to SurePath ™ samples. We will present the results of a 16 month audit and describe the typical characteristics of false negative cases in a medium sized screening laboratory processing approximately 42 000 samples per annum. Cases were identified either from routine rapid screening or by review of negative samples from women with a known high grade CIN lesion. 153 cases were identified: 149 by rapid screening, the remainder by review of the negative samples from women with known CIN. Of those identified by rapid screening 123 were reported as borderline nuclear change, 11 as mild, 4 as moderate, 8 as severe and 3 as CGIN. Only those cases that were found to have a histological lesion were used in the study ( n = 27): Twenty-three were identified by rapid review and a 4 by review of previous negative samples. Six were found to have CIN 1, 7 CIN 2, 13 CIN 3 and 1 CGIN. Examples of the typical characteristics will be demonstrated. Features similar to those observed in conventional smears were identified; scanty abnormal cells (less than 30 per preparation), low contrast samples, pale cells and microbiopsies. In contrast to conventional smears, missed abnormal cells were almost always uniformly scattered throughout the sample. 相似文献
298.
Three new species of the genus BrevitobriusTsalolikhin, 1981 are described. Brevitobrilus glandulatus n. sp. is characterized by conspicuous sphincter between pars dilatata and uterus; two pairs of vaginal glands; spicules having elliptical capitula with small proximal stiffening piece; proximally-arcuate gubernaculum; S3 and S4 smaller than other supplements; S6 out of spicular range and 57-60 micropapillae. Brevitobrilus dimorphicus n. sp. is diagnosed by sexual dimorphism in labial sensilla and amphids; thick-walled rectum with a diverticulum protruding into intestinal lumen and males with boat-shaped spicules and S6 occasionally slightly smaller than other supplements. Brevitobrilus allahabadensis n. sp. possesses large amphids of 28-33% of corresponding labial diameter in both sexes; vagina and uterus with muscular, plicate walls; well developed sphincter between vas deferens and ejaculatory duct; capitulate spicules with sloping ventral and angular dorsal walls; S3, S4 and S6 smaller than other supplements, S6 close to cloaca and 28-37 micropapillae. The relationships of the species of genus Brevitobrilus have been assessed using morphological characters subjected to parsimony and a non cladistic key to identification of species is given. 相似文献
299.
Hans Bakker Takuji Oka Angel Ashikov Ajit Yadav Monika Berger Nadia A. Rana Xiaomei Bai Yoshifumi Jigami Robert S. Haltiwanger Jeffrey D. Esko Rita Gerardy-Schahn 《The Journal of biological chemistry》2009,284(4):2576-2583
In mammals, xylose is found as the first sugar residue of the
tetrasaccharide
GlcAβ1-3Galβ1-3Galβ1-4Xylβ1-O-Ser, initiating the
formation of the glycosaminoglycans heparin/heparan sulfate and
chondroitin/dermatan sulfate. It is also found in the trisaccharide
Xylα1-3Xylα1-3Glcβ1-O-Ser on epidermal growth factor
repeats of proteins, such as Notch. UDP-xylose synthase (UXS), which catalyzes
the formation of the UDP-xylose substrate for the different
xylosyltransferases through decarboxylation of UDP-glucuronic acid, resides in
the endoplasmic reticulum and/or Golgi lumen. Since xylosylation takes place
in these organelles, no obvious requirement exists for membrane transport of
UDP-xylose. However, UDP-xylose transport across isolated Golgi membranes has
been documented, and we recently succeeded with the cloning of a human
UDP-xylose transporter (SLC25B4). Here we provide new evidence for a
functional role of UDP-xylose transport by characterization of a new Chinese
hamster ovary cell mutant, designated pgsI-208, that lacks UXS activity. The
mutant fails to initiate glycosaminoglycan synthesis and is not capable of
xylosylating Notch. Complementation was achieved by expression of a
cytoplasmic variant of UXS, which proves the existence of a functional Golgi
UDP-xylose transporter. A ∼200 fold increase of UDP-glucuronic acid
occurred in pgsI-208 cells, demonstrating a lack of UDP-xylose-mediated
control of the cytoplasmically localized UDP-glucose dehydrogenase in the
mutant. The data presented in this study suggest the bidirectional transport
of UDP-xylose across endoplasmic reticulum/Golgi membranes and its role in
controlling homeostasis of UDP-glucuronic acid and UDP-xylose production.Xylose is only known to occur in two different mammalian glycans. First,
xylose is the starting sugar residue of the common tetrasaccharide,
GlcAβ1,3Galβ1,3Galβ1,4Xylβ1-O-Ser, attached to
proteoglycan core proteins to initiate the biosynthesis of glycosaminoglycans
(GAGs)2
(1). Second, xylose is found in
the trisaccharide Xylα1,3Xylα1,3Glcβ1-O-Ser in
epidermal growth factor (EGF)-like repeats of proteins, such as blood
coagulation factors VII and IX
(2) and Notch
(3)
(Fig. 1). Two variants of
O-xylosyltransferases (XylT1 and XylT2) are responsible for the
initiation of glycosaminoglycan biosynthesis, which differ in terms of
acceptor specificity and tissue distribution
(4-7),
and two different enzymatic activities have been identified that catalyze
xylosylation of O-glucose residues added to EGF repeats
(8-10).
On Notch, O-glucose occurs on EGF repeats in a similar fashion as
O-fucose, which modifications have been shown to influence
ligand-mediated Notch signaling
(11-16).
Recently, rumi, the gene encoding the Notch
O-glucosyltransferase in Drosophila, has been identified,
and inactivation of the gene was found to cause a temperature-sensitive
Notch phenotype (17).
Although this finding clearly demonstrated that O-glucosylation is
essential for Notch signaling, the importance of xylosylation for Notch
functions remains ambiguous.Open in a separate windowFIGURE 1.UDP-xylose metabolism in mammalian cells. A, UDP-Xyl is
synthesized in two steps from UDP-Glc by the enzymes UGDH, forming UDP-GlcA,
and UXS, also referred to as UDP-glucuronic acid decarboxylase. UGDH is
inhibited by the product of the second enzyme, UDP-Xyl
(42). B, in mammals,
UDP-Xyl is synthesized within the lumen of the ER/Golgi, where it is substrate
for different xylosyltransferases incorporating xylose in the
glycosaminoglycan core (XylT1 and XylT2) or in O-glucose-linked
glycans. The nucleotide sugar transporter SLC35D1
(52) has been shown to
transport UDP-GlcA over the ER membrane and SLC35B4
(29) to transport UDP-Xyl over
the Golgi membrane. The function of this latter transporter is unclear.Several different Chinese hamster ovary (CHO) cell lines with defects in
GAG biosynthesis have been isolated by screening for reduced incorporation of
sulfate (18) and reduced
binding of fibroblast growth factor 2 (FGF-2)
(19,
20) and by direct selection
with FGF-2 conjugated to the plant cytotoxin saporin
(21). Isolated cells (called
pgs, for proteoglycan synthesis mutants)
(21) exhibited defects in
various stages of GAG biosynthesis, ranging from the initiating
xylosyltransferase to specific sulfation reactions
(18,
19,
21-25).
Mutants that affect overall GAG biosynthesis were shown to have a defect in
the assembly of the common core tetrasaccharide. Interestingly, these latter
mutants could be separated into clones in which GAG biosynthesis can be
restored by the external addition of xylosides as artificial primers and those
that cannot (18). The two
mutants belonging to the first group are pgsA-745 and pgsB-761. Although
pgs-745 is defective in XylT2
(4-6,
18), pgsB-761 exhibits a
defect in galactosyltransferase I (B4GalT7), the enzyme that catalyzes the
first step in the elongation of the xylosylated protein (25 (see
Fig. 1B). Restoration
of GAG biosynthesis in the latter mutant presumably occurs through a second
β1-4-galactosyltransferase, able to act on xylosides when provided at
high concentration but not on the endogenous protein-linked xylose.Here we describe the isolation of a third CHO cell line (pgsI-208) with the
xyloside-correctable phenotype. The mutant is deficient in UDP-xylose synthase
(UXS), also known as UDP-glucuronic acid decarboxylase. This enzyme catalyzes
the synthesis of UDP-Xyl, the common donor substrate for the different
xylosyltransferases, by decarboxylation of UDP-glucuronic acid. Importantly,
UXS in the animal cell is localized in the lumen of the ER and/or Golgi
(26-28),
superseding at first sight the need for the Golgi UDP-xylose transporter,
which has been recently cloned and characterized
(29). Using this cell variant,
experiments were designed that establish the functional significance of
UDP-Xyl transport with respect to UDP-glucuronic acid production and
xylosylation. 相似文献
300.